1. Nursing Care for a Patient With Multiple Myeloma
Sandra E. Kurtin, RN, MS, AOCN, ANP-C Hematology/Oncology Nurse Practitioner Clinical Assistant Professor of Nursing Clinical Assistant Professor of Medicine Arizona Cancer Center University of Arizona Tucson, Arizona
Welcome. We’re going to talk today about nursing care for a patient with multiple myeloma. My name is Sandy Kurtin. I’m a nurse practitioner and clinical assistant professor of medicine and nursing at the University of Arizona Cancer Center in Tucson, Arizona.
This program is supported by educational grants from

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3. Faculty
Sandra E. Kurtin, RN, MS, AOCN, ANP-C Hematology/Oncology Nurse Practitioner Clinical Assistant Professor of Nursing Clinical Assistant Professor of Medicine Arizona Cancer Center University of Arizona Tucson, Arizona
Disclosure
Sandra E. Kurtin, RN, MS, AOCN, ANP-C, has disclosed that she has received fees for non-CME/CE services from Celgene, Millennium, and Onyx.

4. Introduction: Overview of MM
Let’s start by introducing multiple myeloma.

5. Overproduction of Abnormal Plasma Cells and Associated Serum Proteins in MM
Renal impairment
Cytopenias
MM bone marrow
Myeloid progenitor cell
Invasion of bone marrow
Hematopoietic stem cell
T lymphocytes
Lymphoid progenitor cell
Genetic and molecular defects
MM, multiple myeloma; NK, natural killer.
The primary function of plasma cells is to produce immunoglobulins. These are the basic units from which antibodies are formed. In multiple myeloma, genetic and molecular defects lead to overproduction of abnormal plasma cells and associated serum proteins, or immunoglobulins; this results in a clonal plasma cell malignancy. These molecular and genetic defects occur as a result of complex interactions between the malignant clone and the bone marrow microenvironment, including the bone marrow stroma and various cytokines.
Myeloma cells produce large quantities of 1 abnormal immunoglobulin, or M protein. The most common is IgG, roughly 52% of all multiple myeloma cases; IgA is the second most common, with 21%; IgD is relatively rare, with only 2%; IgE is extremely rare; and then there are light chain only kappa or lambda cases of multiple myeloma, which are roughly 11% of the cases. An overproduction of IgM—roughly 12% of cases with overproduction of immunoglobulins—is rare in multiple myeloma and is typically associated with Waldenström macroglobulinemia. Overproduction of IgM is rare in multiple myeloma and is typically associated with Waldenström macroglobulinemia.
These attributes are key to the presenting signs and symptoms and current approach to treatment for multiple myeloma. The abnormal plasma cells have the ability to infiltrate the bone marrow and bone, producing secondary effects of lytic lesions, hypercalcemia, and cytopenias. In addition, increased levels of circulating myeloma proteins may lead to renal impairment, neurological disease, and immunodeficiency.
NK cells
B lymphocytes
Invasion of bone
↑ circulating abnormal serum proteins
Lytic lesions
hypercalcemia
Immunodeficiency
neurological disease
NIH. Stem cell basics Image created by Sandy Kurtin, The University of Arizona Cancer Center.
Abnormal plasma cells

6. MM Diagnostic Evaluation
History and physical
CBC, differential and platelet count
Additional laboratory tests
Serum immunoglobulins
Quantitative (IgG, IgM, IgA, IgD)
SPEP
SFLC assay (kappa, lambda)
24-hr urine
BUN, creatinine, electrolytes
Serum calcium (corrected)
Serum albumin
β2-microglobulin
LDH
Additional testing based on preliminary analysis
Bone marrow biopsy and aspiration
Hematopathology
Presence of plasma cells, %
Cellularity
Ploidy
Cytogenetics
FISH
Radiology
Skeletal survey
MRI if vertebral compression fractures suspected
PET/CT
Establish diagnosis of MM MGUS Smoldering Active Determine subtype Heavy chain/light chain Nonsecretory Solitary plasmacytoma Determine stage ISS Salmon-Durie staging system Estimate prognosis Cytogenetics Albumin β2-microglobulin Ploidy Identify need for immediate intervention Severe hypercalcemia Acute renal failure Cord compression Severe pain or impending fracture
BUN, blood urea nitrogen; CBC, complete blood count; CT, computed tomography; FISH, fluorescence in situ hybridization; IgG, immunoglobulin G; ISS, International Staging System; LDH, lactate dehydrogenase; MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma; MRI, magnetic resonance imaging; PET, positron emission tomography; SFLC, serum free light chain; SPEP, serum protein electrophoresis.
When looking to diagnose multiple myeloma, we look at laboratory, radiologic, and hematopatholgy to conduct a full evaluation of the patient. Once the diagnosis is made, determination of the stage of disease, the subtype of multiple myeloma based on the individual protein overproduced and including prognostic evaluations, such as cytogenetics, will guide treatment selection. Identification of problems requiring emergent intervention include severe hypercalcemia, acute renal failure, cord compression, and severe pain or impending fracture. For this patient, the MRI of the spine was necessary, given the acute onset of severe pain and a concern for possible cord compression.
NCCN. Clinical practice guidelines in oncology: multiple myeloma. v Kurtin S. JAdPrO. 2010;1:19-29.

7. Aggressive and Stromal Independent Malignant Transformation
MM Disease Trajectory
Nonmalignant Accumulation
Aggressive and Stromal Independent
Malignant Transformation
Plasma cell leukemia
Stroma angiogenesis
and IL-6 dependent
MGUS
Smoldering Myeloma
Multiple Myeloma
< 3 g M protein
< 10% clonal BMPC
No MM-related end-organ damage
1%/yr risk of progression to MM
≥ 30 g/L M protein
≥ 10% clonal BMPC
No MM-related end-organ damage
10%/yr risk of progression to MM in the first 5 yrs
≥ 10% clonal BMPC
M protein in serum and/or urine
≥ 1 CRAB features of disease related to organ damage
C: Calcium elevation > 11.5 mg/L or ULN
R: Renal dysfunction (serum creatinine
> 2 mg/dL)
A: Anemia (Hb <10 g/dL or 2 g < normal)
B: Bone disease (lytic lesions or
osteoporosis)
BMPC, bone marrow plasma cells; Hb, hemoglobin; MGUS, monoclonal gammopathy of unknown significance; M protein, monoclonal protein; IL-6, interleukin-6; ULN, upper limit of normal.
Multiple myeloma has a very heterogeneous outcome: At one end of the spectrum are patients with more aggressive disease that becomes rapidly resistant to available therapies and they die of their disease relatively quickly; at the other end of the spectrum are patients with relatively indolent disease, who may not require treatment or require intermittent therapy and have a lengthy survival. Multiple myeloma is almost always preceded by monoclonal gammopathy of uncertain significance—or MGUS—an asymptomatic phase characterized by a relatively small burden of clonal plasma cells and low levels of monoclonal protein. Patients with MGUS have a small risk of progression relative—approximately 1% per year—to multiple myeloma and require, most often, only observation.
Smoldering multiple myeloma is characterized by a higher burden of malignant plasma cells and a higher level of monoclonal proteins. Although smoldering multiple myeloma has much higher risk of progression to symptomatic myeloma—roughly 10% per year in the first 5 years—many of these patients can be observed for years before any active therapy is required. Given the lack of any demonstrated benefit for initiating therapy for this disease stage, it is important to distinguish this presymptomatic phase from symptomatic myeloma, that requires more immediate therapy.
A diagnosis of active, symptomatic multiple myeloma requires therapy based on end‑organ effects of the disease, and we most often refer to this using the CRAB criteria, which are represented there: the ‘C’ standing for ‘Calcium elevation,’ ‘R’ for ‘Renal dysfunction,’ ‘A’ for ‘Anemia,’ and ‘B’ for ‘Bone disease,’
Kuehl WM, et al. Nat Rev Cancer. 2002;2: Vacca A, et al. Leukemia. 2006;20: Agarwal A, et al. Clin Cancer Res. 2013,19: Durie BG, et al. Hematol J. 2003;4: Adapted with permission from Kurtin SE. J Adv Pract Oncol. 2010;1:19-29.

8. Neither stage I nor stage III
MM Staging Systems
Stage
Durie-Salmon Staging System[1]
International Staging System[2] I
Hemoglobin > 10 g/dL
β2M < 3.5 g/dL and albumin ≥ 3.5 g/dL
Calcium normal or ≤ 12 mg/dL
Normal skeletal survey or solitary plasmacytoma
Low M protein production
IgG < 5 g/dL
IgA < 3 g/dL
Bence Jones protein < 4 g/24 h II
Neither stage I nor stage III
III
1 or more of the following
Hb < 8.5 g/dL
Calcium > 12 mg/dL
Multiple lytic bone lesions
High M protein component
IgG > 7 g/dL
IgA > 5 g/dL
Bence Jones protein > 12 g/24 hrs
β2M ≥ 5.5 g/dL
β2M, β2-microglobulin; Hb, hemoglobin; IgA, immunoglobulin A; M protein, monoclonal protein.
Once the disease is fully staged, we then will look at applying staging systems. There are 2 current systems in use. The Durie Salmon system provides a measure of tumor burden using a number of myeloma‑related bone lesions seen on radiograph, concentrations of serum calcium, monoclonal proteins, and urine Bence‑Jones proteins; and classifies patients into 1 of 3 stages. More recently, the ISS, or International Staging System, has been used, based on measures of proliferative tumor and prognostic information, which was derived by a multivariate analysis of clinical features. And what was found in these studies is that by using the β2-microglobulin and serum albumin levels alone, patients can be effectively categorized into 1 of 3 stages, being I, II, or III.
1. Durie BG, et al. Cancer. 1975;36: Greipp PR, et al. J Clin Oncol. 2005;23:

9. International Staging System
Stage
Characteristic
Median Survival, Mos I
β2M < 3.5 mg/L
Albumin ≥ 3.5 g/dL 62 II
β2M 3.5 to 5.4 mg/L
Albumin < 3.5 g/dL 44
III
β2M ≥ 5.5 mg/L 29
β2M, β2-microglobulin.
You can see here there’s a significant difference in the estimated median survival based on the ISS stage of disease using the β2-microglobulin and serum albumin: stage I with a median survival of just over 5 years; stage II with a median survival of 44 weeks, or 3.6 years; and stage III with a median survival of 29 months, or 2.4 years.
Greipp PR, et al. J Clin Oncol. 2005;23: Kumar SK, et al. Mayo Clin Proc. 2009;84:

10. Risk-Adapted Treatment for MM
MM, multiple myeloma.
Now let’s talk about risk‑adapted treatment for multiple myeloma.

11. Treatment of Multiple Myeloma
Confirmed Diagnosis of Multiple Myeloma—CRAB Criteria
Determination of transplantation eligibility
Immediate interventions for serious adverse events
Individualized Treatment Selection for Induction Therapy
Transplantation Eligible
Works rapidly (CR, nCR, VGPR)
Well tolerated
Spares stem cells
Level of evidence 1 or 2A
Transplantation Ineligible
Achieving a CR or nCR
Tolerability and QoL
PS and comorbidities
CR, complete response; nCR, near complete response; PS, performance score ; QoL, quality of life; VGPR, very good partial response.
Given the heterogeneity of multiple myeloma as a disease and the heterogeneity of the multiple myeloma patient population, a risk-adapted approach to treatment is key. The first priority is to address any urgent patient symptoms or clinical findings. For our patient, treatment of the severe back pain must be a priority.
The next question is one of transplant eligibility. Hematopoietic stem cell transplantation remains an important treatment option for patients with multiple myeloma. A regimen that works rapidly, is well‑tolerated—thus avoiding any irreversible toxicities that may affect transplant eligibility—and one that spares stem cells to allow adequate collection is the goal. Transplant-eligible patients should not receive melphalan‑containing regimens as a part of their induction therapy. Treatment for transplant‑ineligible patients should be effective, well tolerated, and should maintain or improve quality of life. Consideration of performance status and comorbidities, which, together with age, are often the reasons for transplant ineligibility, should be considered in treatment selection.
The duration of treatment for multiple myeloma is highly variable. Continued treatment using salvage therapies for patients with relapsed or refractory multiple myeloma and maintenance therapy following stem cell transplantation will be discussed later in this lecture.
Continued Treatment
Salvage therapy Maintenance therapy
NCCN. Clinical practice guidelines in oncology: multiple myeloma. v

12. Treatment Options Have Greatly Increased in the Past Decade
MM Therapies Introduction
FDA Approved in MM
1950
1960
1970
1980
1990
2000
2010
1983
Autologous
transplantation
1958
Melphalan
2003
Bortezomib 3rd line
2013
Pomalidomide
3rd line
1962
Prednisone
2005
Bortezomib 2nd line
1986
High-dose dexamethasone
2012
Carfilzomib
3rd line
1969
Melphalan +
prednisone
2006
Lenalidomide + dex
2nd line
FDA, US Food and Drug Administration; MM, multiple myeloma; SC, subcutaneous.
The treatment options for patients with multiple myeloma have increased greatly over the last decade. You can see by the diagram in this slide that the left half of the timeline represents 40 years and the right half of the diagram represents 20 years. The number of novel agents and combinations developed in the last 2 decades has changed the treatment paradigm for multiple myeloma. These novel agents have also changed the expected survival for patients with multiple myeloma.
2012
Bortezomib SC
2006
Thalidomide + dex
1st line
2008
Bortezomib frontline
2007
Doxorubicin + bortezomib
2nd line

13. MM Survival Is Improving With Novel Agents
1.0
Median 7.3 yrs
0.9
0.8
0.7
5-Yr Survival by Age, %
0.6
≤ 65 Yrs
> 65 Yrs 73 56 63 31
Proportion of Pts Surviving
0.5
0.4
0.3
0.2
MM, multiple myeloma.
In this slide, we see a study by Kumar and colleagues showing 5-year survival rates from 2006 to 2010 being much better than those for patients treated between 2001 and Importantly, improvement in survival was also seen in the older patients receiving novel agents.
0.1 1 2 3 4 5 6 7 8 9 10
Follow-up From Diagnosis (Yrs)
Kumar SK, et al. ASH Abstract 3972.

14. Changing Treatment Paradigm: Combinations
Common Myeloma Regimens*
Combination
Abbreviation(s)
Bortezomib/dexamethasone
VD or Vd
Bortezomib/cyclophosphamide/dexamethasone
CyBorD
Bortezomib/doxorubicin/dexamethasone
Bortezomib/lenalidomide/dexamethasone
VRD or VRd
Bortezomib/thalidomide/dexamethasone
VTD or VTd
Lenalidomide/dexamethasone
RD or Rd
Carfilzomib/lenalidomide/dexamethasone
Melphalan/ prednisone/bortezomib
VMP or MPB
Melphalan/prednisone/lenalidomide
MPR or MPL
Melphalan/prednisone/thalidomide
MPT
Repeat primary induction (if relapse > 6 mos)
Pomalidomide + dexamethasone (most preferred)
Bortezomib  dexamethasone  lenalidomide
V, VD, Vd, VRD, VRd
Bortezomib/liposomal doxorubicin
Carfilzomib
Cyclophosphamide/lenalidomide/dexamethasone
Dexamethasone/cyclophosphamide/etoposide/cisplatin
DCEP
Dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophos phamide/etoposide  bortezomib
DT-PACE VTD-PACE
High-dose cyclophosphamide
Thalidomide/dexamethasone
TD or Td
Rationale: combination therapies demonstrated improved response rates, PFS, and/or OS compared with single agents
Nursing considerations
AE management
Patient adherence
Performance status
Frailty
Renal function
Other comorbidities
Patient preference
See clinicaloptions.com/OncTools for treatment tool
Transplant
Primary Induction
Non-transplant
AE, adverse event; PFS, progression-free survival; OS, overall survival.
There are a number of treatment options available for patients, based on individual risk stratification. Combination therapies using novel agents have demonstrated improved rates, progression‑free survival, and overall survival compared with single agents. For all patients, the common adverse events profiles, renal and hepatic function, protocol intensity and patient-caregiver requirements, performance status, comorbidities, and frailty should be considered in deciding the best treatment for each patient. The patient and caregiver preference must also be considered. You can access a treatment tool at clinicaloptions.com/onctools for a useful pocket guide that addresses many of these items.
Salvage Regimens
*Preferred regimens according to NCCN. Clinical practice guidelines in oncology: multiple myeloma. v

15. Common Dosing Regimens for Novel Therapies
Agent/Class
Dosing and Route of Administration
Bortezomib[1]/
proteasome inhibitor
1.3 mg/m2 IV or SC on Days 1, 4, 8, 11, every 21 days x 2 cycles, then weekly dosing 3 wks on/1 wk off
Variable dosing in combination regimens
Dose modification for neuropathy, cytopenias
Carfilzomib[2]/
20 mg/m2 IV (cycle 1), 27 mg/m2 (cycles 2-12) on Days 1, 2, 8, 9, 15, 16, every 28 days
Dose modifications for cytopenias, cardiopulmonary symptoms
Lenalidomide[3]/
immunomodulatory agent
25 mg/day by mouth for induction
Dose modification based on renal function, cytopenias
Pomalidomide[4]/
4 mg/day on Days 1-21 using a 28 day cycle
Dose modifications for cytopenias
Thalidomide[5]/
200 mg/day by mouth at bedtime
IV, intravenous; SC, subcutaneous
Each drug has FDA-approved dosing guidelines based primarily on the registration trials. Since approval, many of these agents have been combined or used in alternative dosing schedules. It is important to refer to recent references for these alternative dosing regimens, and you can find some of these examples on the Clinical Care Options Web site.
1. Bortezomib [package insert]. 2. Carfilzomib [package insert]. 3. Lenalidomide [package insert]. 4. Pomalidomide [package insert]. 5. Thalidomide [package insert].

16. Risk-Stratification Based on Tumor Biology
High Risk*
Intermediate Risk
Standard Risk
17p deletion
t(14;16) (C-MAF)
t(14;20) (MAF-B)
High-risk GEP signature
t(4;14) (FGFR3/MMSET)
All others including
Hyperdiploidy
t(11;14) (CCND1)
t(6;14) (CCND3)
*Presence of trisomies ameliorates high risk.
Certain cytogenetic findings are considered high risk, as noted above. For these patients, achieving a complete response or better is considered critical to improving overall survival. Regimens incorporating novel agents are recommended. Based on data from trials and induction therapies, a bortezomib‑containing regimen is recommended for patients with the translocation 4;14, as for the patient in our case study. Patients with standard-risk cytogenetics generally respond well to novel therapies.
Complete Response appears critical
Bortezomib critical
Excellent outcome with novel agents
Rajkumar SV. Am J Hematol. 2012;87: Moreaux J, et al. Hematologica. 2011;96:

17. Common Disease-Related and Treatment-Emergent Adverse Events
Myelosuppression*; all agents
Anemia, neutropenia, thrombocytopenia
Renal toxicities*
Hepatic toxicities
Neurotoxicity*
Nausea and vomiting
Constipation or diarrhea
Pain
Infection
Drug-specific treatment-emergent adverse events
The most common treatment‑emergent adverse events for patients receiving treatment for multiple myeloma are listed here. It is important to note that selected symptoms may also be disease related. For example, anemia is a common presenting symptom for patients with newly diagnosed multiple myeloma and is part of the CRAB criteria. Evaluating each patient at baseline for symptoms and following these over the course of their disease and treatment is important. Understanding the individual drug profiles will be necessary to tailor the therapy for each patient.
*May also be disease related.
Kurtin SE, et al. J Adv Pract Oncol In press.

18. PIs: Common Adverse Events in MM Trials
Adverse Events > 5% to 10%,
All Grades (Grade 3/4), %
Bortezomib
Carfilzomib Relapsed/Refractory
Thrombocytopenia and neutropenia
Thrombocytopenia (cyclic): 36 (29)
Neutropenia: 17; (12)
Thrombocytopenia: (cyclic): 36.3 (23.4)
Neutropenia: 20.7 (10.3)
Peripheral neuropathy
Twice weekly IV: 53 (16)
Weekly IV: 41 (16)
Weekly SC: 24 (6)
Overall: 14 (1% grade 3, no grade 4)
Fatigue
Overall: 64 (16)
Overall: 55.5 (7.6)
Gastrointestinal
Diarrhea:
Overall: 52 (8)
Nausea: 57 (8)
Constipation: 20.9 (0.2)
Diarrhea: 32.7 (1.0)
Nausea: 44.9 (1.3 )
Cardiopulmonary
Dyspnea: 11, (3)
Hypotension: 13
Congestive heart failure: 5
Peripheral edema: 11
Dyspnea: 34.6 (5.1)
Hypertension: 14.3 (3.3)
Peripheral edema: 24.0 (0.6)
Infectious complications
Varicella zoster: 13-20
Varicella zoster: 2
Pneumonia: 12.7 (10.5)
Renal dose modification
No renal dose adjustment required
Renal dose adjustment recommended for creatinine ≥ 2 x baseline
Thromboembolic events
Not reported*
Rash
MM, multiple myeloma; PI, proteasome inhibitor.
So, let’s talk a little bit about the common adverse events in multiple myeloma trials, and these are tables that present data for both immunomodulatory agents and proteasome inhibitors. So, on this slide you see the proteasome inhibitors, and it is important to know the difference in drug profiles within each class. In the case of bortezomib, the root of administration—IV vs subcu—can also make a difference in the incidence and severity of side effects, in particular peripheral neuropathy.
*Data not available or incidence was below threshold for reporting.
Bortezomib [package insert]. Carfilzomib [package insert]. Palumbo A, et al. N Engl J Med. 2011;364: Kurtin SE, et al. J Adv Pract Oncol In press.

19. IMiDs: Common Adverse Events in MM Trials
Adverse Events > 5% to 10%, All Grades (Grade 3/4), %
Lenalidomide (With Dexamethasone)
Thalidomide (With Dexamethasone)
Pomalidomide 4 mg* (With Dexamethasone) Relapsed/Refractory
Thrombocytopenia and neutropenia
Thrombocytopenia: 21 (12)
Neutropenia: 42 (33)
Thrombocytopenia: 23
Neutropenia: 31
Thrombocytopenia: 23 (19 ) Neutropenia: 47 (38)
Peripheral neuropathy
Not significant
All grades: 54 (3-5)
↑ with higher doses and prolonged therapy
Overall: 7 (0)
Fatigue
Overall: 43 (6)
Overall: 81 (17)
Overall: 63 (13)
Gastrointestinal
Constipation: 40 (3)
Diarrhea: 38.5 (2)
Nausea: 26 (1)
Constipation: 56 (8)
Nausea: 29 (5)
Diarrhea: 33 (0)
Anorexia: 35 (0)
Nausea: 22 (0)
Cardiopulmonary
Dyspnea: 23 (not reported)
Hypotension: 7 (not reported)
Dyspnea: 41 (13)
Peripheral edema: 57 (6)
Bradycardia reported
Dyspnea: 45 (13)
Peripheral edema: 16 (0)
Infectious complications
Pneumonia: 14
Pneumonia: 35
Pneumonia: 29 (23)
Renal dose modification
Requires renal dose adjustment
No dose modification required
Dose modification should be considered if creatinine > 3.0; clinical trial in renal impairment under way
Thromboembolic events
Overall: 9.3
Overall: 23
Not reported*
Rash
Overall: 21
Overall: 30
Overall: 16
IMiD, immunomodulatory drug; MM, multiple myeloma.
The immunomodulatory agents have varying AE profiles, as well. Thalidomide is associated with peripheral neuropathy, whereas lenalidomide and pomalidomide are not likely to cause peripheral neuropathy.
*Data not available or incidence was below threshold for reporting.
Lenalidomide [package insert]. Thalidomide [package insert]. Pomalidomide [package insert]. Palumbo A, et al. N Engl J Med. 2011;364: Kurtin SE, et al. J Adv Pract Oncol In press.

20. How to Select Therapy for the Older Adult?
Goals of therapy
Early and sustained CR with an acceptable level of toxicity and improved QoL
Risk stratification including transplantation eligibility and individual patient factors
Disease-Related Factors
Patient-Related Factors
High tumor burden
Renal failure
Hypercalcemia
Fractures
Fit vs frail/vulnerability
Comorbidities: controlled vs uncontrolled
Clotting or bleeding history
Preexisting neuropathy
Patient wishes
Availability of a caregiver
CR, complete response; QoL, quality of life.
We’re going to talk about a few other options in terms of peripheral neuropathy and bortezomib. Let’s talk first about how to select therapy for the older adult. Additional considerations when selecting treatment include age‑related factors, performance status, and comorbidities; however, chronological age alone should not exclude treatment, although there are specific criteria for auto-autologous stem cell transplantation. As with all patients of any age, high-risk disease‑related factors should be considered. Having an available caregiver is particularly important for the older patient.
Niesvizky R, et al. Oncology. 2010;24: NCCN. Clinical practice guidelines in oncology: multiple myeloma. v Stadtmauer EA. Oncology. 2010;24:7-13.

21. Functional Status, Comorbidities, Frailty, and Vulnerability
Functional status: measured by ECOG and Karnofsky PS
ADLs: ability to bathe, dress, toilet and maintain continence, transfer, and eat independently
IADLs: finances, shopping, housekeeping, transportation, and self-medication
Comorbidities
Cardiovascular, renal, hepatic, pulmonary, endocrine, rheumatologic disease, and other cancers
Number, severity, controlled or uncontrolled
ADLs, activities of daily living; ECOG, Eastern Cooperative Oncology Group; IADLs, instrumental activities of daily living; PS, performance status.
Evaluation of performance status is a standard requirement for patients considering a clinical trial. This is based on data showing that patients with a poor performance status do not tolerate treatment; however, assessment of performance status is somewhat subjective, based on patient self‑report of brief episodic encounters in the clinical setting. It is important to get feedback from caregivers and to evaluate a patient over a series of visits to better characterize performance status.
Palumbo A, et al. Blood. 2011;118: Kumar S, et al. CA Cancer J Clin. 2010;60: Balducci L, et al. Oncologist. 2000;5:

22. Functional Status, Comorbidities, Frailty, and Vulnerability
Weight loss, weakness, poor nutritional intake, cognitive impairment, and poor endurance
Cardiovascular Health Study (n = 5317): frailty associated with hospitalization, falls, declining ADLs including diminished mobility, and death (P < .0001)
Vulnerability
A complex of comorbidity (presence of chronic diseases or conditions), disability (physical or mental impairment), and frailty (fatigue, low activity) that could prevent adequate therapy
ADLs, activities of daily living.
More recently, evaluation of comorbidities has become standard in the treatment setting, in particular for transplants. The severity, duration, effective or ineffective management and number of organ systems involved will affect the patient’s tolerance of therapy. The concept of frailty has also been emphasized more recently; determining whether a patient is fit or frail is an important clinical consideration. Frailty is what I like to refer to as, “The withering syndrome”: the patient is losing weight, becoming weaker and may not be able to maintain simple daily tasks. Vulnerability, a term Dr Palumbo and others have developed, looks at all of these concepts: comorbidity, fit or frail, and any disability in evaluating patients for treatment and particular transplant.
Palumbo A, et al. Blood. 2011;118: Kumar S, et al. CA Cancer J Clin. 2010;60: Balducci L, et al. Oncologist. 2000;5:

23. Dose Adjustments for Age/Frailty
Drug
No Risk Factors*
At Least 1 Risk Factor*
At Least 1 Risk Factor* + Grade 3-4 Nonhematological AE
Bortezomib
1.3 mg/m2 biweekly Days 1, 4, 8,11 q3w
1.3 mg/m2/wk
Days 1, 8, 15, 22 q5w
1.0 mg/m2/wk
Lenalidomide
25 mg/day
Days 1-21 of 28-day cycle
15 mg/day
10 mg/day
Dexamethasone
40 mg/day
Days 1, 8, 15, 22 q4w
20 mg/day
Melphalan
0.25 mg/kg or 9 mg/m2
Days 1-4 q4-6w
0.18 mg/kg or 7.5 mg/m2
0.13 mg/kg or 5 mg/m2
Thalidomide
100 mg/day
50 mg/day
50 mg QOD
AE, adverse event; q3w, every 3 weeks; q4w, every 4 weeks; q4-6w, every 4-6 weeks; q5w, every 5 weeks; QOD, every other day.
Dr Palumbo and colleagues have also proposed dose-adjustment guidelines for age and frailty. For our patient, this may mean using different doses for RVD, and I’ve highlighted these in yellow, here, based on the patient’s age and comorbidities.
*Dosing based on risk factors including age, comorbidities, controlled vs uncontrolled. Patients grouped from very fit to severely frail, depending on need for help and level of activity.
Palumbo A, et al. Blood. 2011;118: 23

24. Recommendations for Adjunctive Treatment
Bone disease*
Bisphosphonates
Monitor for osteonecrosis
Renal dosing required
Treat for 2 yrs
Radiation therapy
Orthopedic consultation
Vertebroplasty or kyphoplasty
Hyperviscosity
Plasmapheresis
Hypercalcemia
Hydration, steroids, furosemide
Zoledronic acid preferred bisphosphonate
Anemia
Consider erythropoietin
Caution in patients at high risk for thrombosis
Transfusion
Coagulation/thrombosis
Prophylactic anticoagulation if treated with IMiDs
IMiD, immunomodulatory drug.
Let’s talk a little bit about the recommendations for adjunctive treatment. Several are recommended for the patient with multiple myeloma. These treatments may include interventions to address immediate clinical findings or symptoms or may be used to prevent potential complications, such as skeletal‑related events or thrombosis.
*Included in the International Myeloma Foundation Nursing Leadership Board Survivorship Plan for MM
NCCN. Clinical practice guidelines in oncology: multiple myeloma. v Miceli TS, et al. Clin J Oncol Nurs. 2011;15:9-23. Faiman BM, et al. Clin J Oncol Nurs. 2011;15:66-76.

25. Recommendations for Adjunctive Treatment
Infection
IVIG for recurrent infections
Pneumococcus and influenza vaccines
PCP, herpes, and antifungal prophylaxis for high-dose or long-term steroids
Herpes zoster prophylaxis for bortezomib-treated patients
No live zoster vaccine
Renal dysfunction*
Dose modifications for selected regimens
Avoid aggravating factors: contrast, NSAIDs, dehydration
Not a contraindication to HSCT
Monitor bisphosphonates
Neuropathy
Requires dose adjustment for selected agents
Bortezomib SC vs IV
Baseline, ongoing monitoring
HSCT, hematopoietic stem cell transplantation; IV, intravenous; IVIG, intravenous immunoglobulin; NSAID, nonsteroidal antiinflammatory drug; PCP, Pneumocystis carinii pneumonia; SC, subcutaneous.
Infections are more common and are the leading cause of morbidity and mortality in multiple myeloma. Prevention of infection should include immunizations for pneumonia and influenza; however, the zostavax vaccine, which is a live virus, should not be administered to multiple myeloma patients. Patients at risk for herpes zoster, such as those taking proteasome inhibitors, should receive prophylactic antiviral treatment, such as acyclovir or valganciclovir.
*Included in the International Myeloma Foundation Nursing Leadership Board Survivorship Plan for MM
NCCN. Clinical practice guidelines in oncology: multiple myeloma. v Miceli TS, et al. Clin J Oncol Nurs. 2011;15:9-23. Faiman BM, et al. Clin J Oncol Nurs. 2011;15:66-76.

26. Bortezomib: SC vs IV Administration
Subcutaneous (SC)
FDA approved SC in 2012
Equivalent efficacy as IV (numerous studies)
Reduced neuropathy, GI AEs
67.8% of patients prefer SC over IV
54 min less “chair time” on average
46 min less clinic time on average
Intravenous (IV)
FDA approved IV in 2003
Highly effective myeloma therapy
Neuropathy a notable AE
Reconstituting bortezomib (3.5 mg vial)
For SC administration,
add 1.4 mL
0.9% sodium chloride
AE, adverse event; FDA, US Food and Drug Administration; GI, gastrointestinal; IV, intravenous; SC, subcutaneous.
Let’s first talk about other ways to reduce the incidence and severity of peripheral neuropathy. Two recent noninferiority trials investigating the administration of bortezomib using either IV or subcutaneous routes showed an equal therapeutic benefit with a reduction in the incidence and severity of peripheral neuropathy. Administrating additional IV fluids can minimize hypotension, also sometimes seen with bortezomib administration. Importantly, reconstitution of the drug is different for each route of administration, and so deciding on the route prior to mixing the drug is very important.
For IV administration,
add 35 mL
0.9% sodium chloride
Hydration: a key nursing consideration, especially in patients with renal compromise
Shah GL, et al. ASH Abstract Barbee MS, et al. ASCO Abstract E Moreau P, et al. ASH Abstract Moreau P, et al. Lancet Oncol. 2011;12: Bortezomib [package insert].

27. Phase III Study: Subcutaneous vs Intravenous Bortezomib
Route and Administration
ORR, %
CR, %
Median Time to Response,
Mos
Median TTP, Mos PN
All Grades, %
Grade 3/4, %
IV (n = 73) 42 8
1.4
9.4 53 16
SC (n = 145) 6
10.4 38
P value
.387
.044
.026
SC administration of bortezomib noninferior to IV (P = .002)
Improved safety profile with bortezomib SC vs IV
CR, complete response; IV, intravenous; ORR, overall response rate; PN, peripheral neuropathy; SC, subcutaneous; TTP, time to progression.
You can see here the efficacy of IV vs subcutaneous bortezomib being equal, however, with a significant reduction in the rate of peripheral neuropathy using the subcutaneous route.
Moreau P, et al. Lancet Oncol. 2011;12: Bortezomib [package insert].

28. SC Bortezomib: Site Selection
SC Injection-Site Selection
Adequate adipose tissue: “pinch an inch” using index finger and thumb
Rotate sites, minimum of 1 cm apart
Avoid: 2-cm region surrounding the umbilicus, areas prone to friction (eg, belt-line, seatbelt region, etc), injecting into areas with scarring, birthmarks, inflammation, hair follicles, or impaired skin integrity
Front
Back
Sites for SC bortezomib
Not studied for SC bortezomib
SC, subcutaneous.
Subcutaneous administration of chemotherapy, including bortezomib, may be associated with injection site reactions. It is important to consider the length of the needle, proper technique, angle of entry into the skin, and the thickness of the subcutaneous tissue in different regions of the body, as seen here in this diagram and chart. Importantly, the trials for bortezomib did not evaluate the back of the arm as an injection site, so there is no pharmacokinetic data. Roughly 6% of patients had injection site reactions, including itching, swelling, pain or redness, with a median of 6 days to resolution.
SC Thickness in Adults, mm
Male
Female
Upper arm* 9 15
Abdomen
14 (2-30)
23 (6-58)
Thigh
7 (2-22)
14 (5-34)
~ 6% patients had injection site reactions (itching, swelling, pain, and/or redness); median 6 days to resolve
*Not included in pharmacokinetic studies for SC bortezomib.
Kurtin S, et al. J Adv Pract Oncol. 2012;3: Bortezomib [package insert].

29. SC Bortezomib: Air Sandwich Technique
Attach fresh needle (4-6 mm) to syringe with prepared medication
Do not purge needle (air in needle)
Maximum volume for SC injection is 2 mL per site
Pull mL air into syringe
Use index finger and thumb to “pinch an inch”—avoid pinching the underlying muscle
Invert syringe and inject, including air behind the drug
90° angle for 4- to 6-mm needles
45° angle for ≥ 8-mm needle
Remove needle promptly
Apply gentle pressure to site
SC, subcutaneous.
The other strategy used to minimize injection site reactions is an injection technique called “The air sandwich.” This technique minimizes the exposure of the subcutaneous tissue to any chemotherapy during the injection or withdraw of the needle. When needles are purged after drawing up the medication, a small amount of drug is exposed at the bevel of the needle; this drug can be tracked through the tissue, causing irritation. By drawing a small amount of air into the syringe after drawing up the medication, when the syringe is inverted the air will follow the drug and will fully clear the needle of drug, essentially locking the drug into the subcutaneous tissue and minimizing drug contact with removal of the needle from the tissue.
Use “air sandwich” technique to avoid seeding of irritating medication in the injection track
Kurtin S, et al. J Adv Pract Oncol. 2012;3:

30. Thromboembolic Events
Cancer patients are at increased risk of TEE (4- to 5-fold)
Risk of mortality from a TEE is 2-fold higher in cancer patients
Individuals with advanced disease are at higher risk of TEE
Myeloma patients at highest risk at time of initial diagnosis
TEE, thromboembolic events.
Thromboembolic events are not uncommon in cancer patients. Patients with multiple myeloma are thought to have an increased risk of clotting, in part due to the overproduction of interleukin‑6. Patients with higher risk disease and those with more bulky disease are at the greatest risk. Thromboprophylaxis is recommended for any multiple myeloma patient at risk for clotting.
Kristinsson SY. Hematology Am Soc Hematol Educ Program. 2010;2010: Boyle EM. Expert Rev Hematol. 2012;5:

31. Thromboprophylaxis: Thalidomide, Lenalidomide, and Pomalidomide
Individual Risk Factors
Actions
Obesity
Previous VTE
Central venous catheter, pacemaker
Associated diseases
Cardiac
Chronic renal disease
Diabetes
Acute infection
Immobilization
Blood clotting disorders
Surgery, anesthesia, or trauma
Medications
ESAs
LMWH (enoxaparin 40 mg/day or equivalent)
Warfarin (target INR: 2-3)
Myeloma-Related Risk Factors
Diagnosis
Hyperviscosity
Myeloma therapy
High-dose dexamethasone
Doxorubicin
Multiagent chemotherapy
In general:
Low risk (1 risk factor): patient should receive ASA mg/day
High risk: patient should receive therapeutic prophylactic anticoagulation with LMWH, warfarin
MYELOMA IS A RISK FACTOR
ASA, acetylsalicylic acid; ESA, erythropoiesis stimulating agent; INR, international normalized ratio; LMWH, low molecular weight heparin; VTE, venous thromboembolism.
The immunomodulatory agents thalidomide, lenalidomide, and pomalidomide have been associated with an increased risk of thromboembolic events; when given with high-dose dexamethasone, this risk is substantially higher. To prevent thrombosis, patients should be evaluated for risk factors, keeping in mind having multiple myeloma itself is a risk factor. For patients with more than 2 risk factors, full anticoagulation is recommended. Patients at lower risk can be placed on 81 mg of aspirin daily. The patient in our case has more than 2 risk factors—diabetes, hyperlipidemia, obesity, lenalidomide, and having multiple myeloma—therefore, she should be treated with full anticoagulation.
Trujillo Santos AJ. Med Clin. 2012;139: Boyle EM, et al. Expert Rev Hematol. 2012;5: Larocca A, et al. Blood. 2012;119:

32. Nursing Considerations for the Patient With Relapsed or Relapsed/Refractory MM
MM, multiple myeloma.
So, let’s talk a little bit about nursing considerations for the patient with relapsed or relapsed refractory multiple myeloma.

33. MM as a Chronic Disease MM patients are living longer
Patients will be exposed to multiple therapies over the course of their disease
AHSCT remains an important treatment option but is not curative in the majority of patients
Relapse or progression is inevitable for most patients
Patients who fail first-line novel agents have a poor prognosis (~ 9 mos from time of relapse)
Response to salvage therapy for relapsed and refractory MM may be as short as 6 mos
AHSCT, autologous hematopoietic stem cell transplantation; MM, multiple myeloma.
The good news is that patients are living much longer with multiple myeloma. Unfortunately, relapse or progression is inevitable in the majority of patients. Patients who fail first-line novel agents do poorly, and responses to salvage therapy may be as little as 6 months. So, most patients will receive all available therapeutic agents over the course of their disease, and many will have 1 or more transplants
Kumar SK, et al. Leukemia : Richardson PG, et al. Oncology. 2010;24:22-29.

34. Natural History of Multiple Myeloma
Asymptomatic
Symptomatic
100
2. Relapse
Active myeloma
Refractory relapse
M Protein (g/L)
1. Relapse 50
MGUS or smoldering myeloma
Plateau remission 20
M protein, monoclonal protein; MGUS, monoclonal gammopathy of undetermined significance.
This cartoon shows a typical trajectory for a patient with multiple myeloma: multiple relapse with a reduction in the depth and duration of response over time. This emphasizes the desired goal for early depth of response in induction therapies and maintaining therapies over longer periods of time to maintain that duration of response.
First-line therapy
Second-line therapy
Third-line therapy
Kuehl WM, et al. Nat Rev Cancer. 2002;2: Vacca A, et al. Leukemia. 2006;20: Siegel DS, et al. Community Oncol. 2009;6:12: Durie BG, et al. Hematol J. 2003;4: Adapted with permission from Durie B at 34

35. Clonal Evolution and Clonal Competition
Len/Dex
Multiple clones may be present at the time of diagnosis
The predominant clone may change over time, especially after treatment rounds
31%
64%
21% 9%
64%
Remission ~ 2N
Len/Dex
Relapse 1 ~ 2N
Carfilzomib
Clone 1.1 Clone 1.2 Clone 2.1 Clone 2.2 Misc
Hypothesis: effective treatment reduces or eliminates the dominant clone; however, other clones can still exist
Relapse 2 ~ 2N
10%
Diagnosis ~ 2N
19%
11%
58%
72%
Bortezomib SGN-40
Relapse 3 ~ 2N
17%
Relapse can occur when:
Existing clone no longer has to compete for space with the formerly dominant clone
Acquires additional mutation(s) providing a growth and/or survival advantage
clg-high 66%
Len/Dex, lenalidomide/dexamethasone; MPV, melphalan/prednisone/bortezomib.
A recent publication by Keats et al suggests that multiple clones may be present at the time of diagnosis of multiple myeloma. The predominant clone may change over time, especially after treatment rounds. The hypothesis is that effective treatment reduces or eliminates the dominant clone; however, other clones can still exist, and relapse can occur when the existing clone no longer has to compete for space with the formerly dominant clone or acquires additional mutations, providing a growth or survival advantage.
71%
clg-high 37%
95%
78%
MPV
Plasma cell leukemia ~ 3N
Relapse 4 ~ 3N
clg-low 34%
clg-low 63%
96%
96%
Keats JJ, et al. Blood. 2012;120: 35

36. Relapsed and Relapsed/Refractory MM
Relapse: development of clinically measurable disease or secondary organ effects after achieving a CR
Progression: development of clinically measurable signs of increased disease activity after achieving a PR or disease plateau
Progression of disease is implied in the term “relapsed”
Relapsed and refractory: defined as a lack of response or disease progression on or within 60 days of the last therapy
The therapy in use at the time of progression is what the patient is refractory to based on the dominant clone
Primary refractory: failure to achieve any response to specific MM treatments, often 2 or 3 novel agent combination regimens
CR, complete response; MM, multiple myeloma; PR, partial response.
So, let’s go over a few of the definitions when we talk about relapsed and refractory multiple myeloma. So clonal evolution is thought to play a role in the development of relapse and refractory multiple myeloma. It’s important to know that not every patient with relapsed multiple myeloma will be the same. Some patients will have an early relapse soon after their initial therapy; other patients, it may be years. Relapse refractory multiple myeloma has a very specific definition, and it’s important to familiarize yourself with the definitions of relapse, progression, relapse refractory, or primary refractory multiple myeloma to better understand how to best select the next therapy for your patient.

37. Salvage Therapy
So, let’s talk about salvage therapy, then.

38. MM Salvage Therapy: Clinical Guidelines
Proteosome Inhibitor–Containing Regimens
Bortezomib
Bortezomib (category 1) Bortezomib/liposomal doxorubicin (category 1) Lenalidomide/bortezomib/dexamethasone Bortezomib/dexamethasone Cyclophosphamide/bortezomib/dexamethasone Dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide/ bortezomib
Carfilzomib
Single-agent carfilzomib*
IMiD-Containing Regimens
Lenalidomide
Lenalidomide/bortezomib/dexamethasone Lenalidomide/dexamethasone (category 1)
Pomalidomide
Pomalidomide*/dexamethasone
Thalidomide
Thalidomide/dexamethasone
Other regimens
Dexamethasone/cyclophosphamide/etoposide/cisplatin Dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide
IMiD, immunomodulatory drug; MM, multiple myeloma; NCCN, National Comprehensive Cancer Network.
The drugs used for salvage therapy include the novel agents used in earlier line therapy with the addition of 2 new agents: carfilzomib and pomalidomide.
*Indicated for patients with MM who have received ≥ 2 previous therapies (including bortezomib and an IMiD) and have progressed on/within 60 days of completing last therapy.
Kurtin SE, et al. J Adv Pract Oncol In press. NCCN. Clinical practice guidelines in oncology: multiple myeloma. v

39. Considerations in Selecting Salvage Therapy
Time from previous therapy to relapse or progression
> 6 mos may use similar agents
< 6 mos: consider alternative agents in combination
Refractory disease
Clinical trial enrollment
Newly FDA-approved agents pomalidomide or carfilzomib
Reassess transplantation options, including alloSCT on clinical trial
Previous ASCT: second ASCT if TTP > 2 yrs
Agents based on
Time from previous therapy to relapse/progression
Any residual clinical conditions (neuropathy, renal function, etc)
Previous thalidomide
Bortezomib or bortezomib/PLD
Len/dex
High-dose dexamethasone/carfilzomib/pomalidomide
Previous bortezomib
Thalidomide
Lenalidomide
Bortezomib/carfilzomib/pomalidomide
Previous lenalidomide
Bortezomib
Bortezomib/PLD
Carfilzomib/pomalidomide
AlloSCT, allogeneic stem cell transplantation; ASCT, autologous stem cell transplantation; PLD, pegylated liposomal doxorubicin; TTP, time to progression.
When selecting a salvage therapy, it is necessary to assess what the patient has previously been treated with; what was the depth and duration of response; how was the treatment tolerated; and were there any residual toxicities?
Richardson PG, et al. Oncology. 2010;24: NCCN. Clinical practice guidelines in oncology: multiple myeloma. v

40. Treatment Paradigm Shift: Maintenance vs Continuous Therapy
IMWG Consensus on Maintenance Therapy
Drug
Common Dose or Regimen
Duration
Tolerance
Comments
Lenalidomide
10* (5-15) mg/day
continuously or on Days 1-21, every 28 days
Until PD or intolerance
Few discontinuations due to AEs
Unprecedented extension of PFS, increased OS in 1 of 3 studies; generally well tolerated, but risk of second malignancies increased
Bortezomib
1.3 mg biweekly
2 yrs or until PD or intolerance
Grade 3/4 PNP: 16% (IV administration)
Only comparison between PAD–ASCT bortezomib and VAD–ASCT thalidomide available
Thalidomide
50* (100) mg/day
Up to 1 year; no correlation between duration and outcome
PNP, fatigue, and other limiting dose and duration of therapy
Poor tolerance in some patients (notably in elderly); no benefit in patients with FISH-defined high-risk profile
AE, adverse event; ASCT, autologous stem cell transplantation; FISH, fluorescence in situ hybridization; IMWG, International Myeloma Working Group; IV, intravenous; OS, overall survival; PAD, bortezomib, adriamycin, and dexamethasone; PD, progressive disease; PFS, progression free survival; PNP, peripheral neuropathy; VAD, vincristine, adriamycin, and dexamethasone.
One of the more recent shifts in the treatment paradigm for multiple myeloma has been the addition of maintenance therapy following autologous stem cell transplant, the goal being continued suppression of the malignant clone or clones, knowing that even with an autologous transplant, most patients with multiple myeloma will relapse. Ongoing trials are evaluating a number of novel agents in this setting; Lenalidomide and bortezomib with or without dexamethasone have been studied most extensively.
*Recommended
Adapted from Ludwig H, et al. Blood. 2012; 119:

41. Natural History of Multiple Myeloma
Asymptomatic
Symptomatic
100
2. Relapse
Active myeloma
Refractory relapse
M Protein (g/L)
1. Relapse 50
MGUS or smoldering myeloma
Plateau remission 20
M protein, monoclonal protein; MGUS, monoclonal gammopathy of undetermined significance.
So, if we look again at the disease trajectory, we can see now in the far right that we’re talking now about a relapse refractory population and that the depth of responses and the duration of responses become much shorter.
First-line therapy
Second-line therapy
Third-line therapy
Kuehl WM, et al. Nat Rev Cancer. 2002;2: Vacca A, et al. Leukemia. 2006;20: Siegel DS, et al. Community Oncol. 2009;6:12: Durie BG, et al. Hematol J. 2003;4: Adapted with permission from Durie B at 41

42. Relapsed and Refractory MM: General Principles
Treatment of patients with relapsed and refractory MM is complicated by the heterogeneity of the disease as well as adverse events of MM treatments
As proteasome inhibitors and IMiDs are now used more frequently in the upfront setting, novel salvage therapies are needed that are efficacious and well tolerated
2 novel agents have recently been approved
Pomalidomide
Carfilzomib
IMiD, immunomodulatory drug; MM, multiple myeloma.
Treatment of patients with relapse and refractory multiple myeloma is complicated by the heterogeneity of the disease, as well as the side effects of multiple myeloma treatments. As proteasome inhibitors and immunomodulatory agents are now used more frequently in the upfront setting, novel salvage therapies are needed that are effective and well tolerated. Two novel agents have recently been approved: pomalidomide and carfilzomib.

43. Newly Approved Agents: Pomalidomide
FDA approved: February 8, Class: IMiD Administration: oral
REMS program
Discuss administration with patient : 4 mg once daily on Days 1-21 of 28-day cycle
Take without food
At least 2 hrs before/after meals
Do not break, chew, or open the capsules
Adherence: consistent schedule (AM or PM)
Pomalidomide Common AEs (in > 30%)
Patients, %
Fatigue and asthenia 55
Neutropenia 52
Constipation 36
Nausea
Diarrhea 34
Dyspnea
Upper resp. tract infection 32
Back pain
Pyrexia (pom + dex) 30
AE, adverse event; Dex, dexamethasone; DVT, deep vein thrombosis; FDA, US Food and Drug Administration; IMiD, immunomodulatory drug; Pom, pomalidomide; PN, peripheral neuropathy; REMS, Risk Evaluation and Mitigation Strategy.
So let’s talk a little bit about these 2 new novel agents. The first of these, pomalidomide, was approved in February of It is the newest immunomodulatory agent, and it does require a safety program for dispensing similar to those used for lenalidomide. It should be taken without food, and the toxicity profile is similar to lenalidomide.
Educate patients on
DVT prophylaxis
Infection risk/blood counts
Fatigue
Should not cause PN
Pomalidomide [package insert]. FDA.gov

44. Newly Approved Agents: Carfilzomib
FDA approved: July 20, Class: proteasome inhibitor Administration
Premedicate: 4-mg dexamethasone before carfilzomib
All doses cycle 1; 1st dose cycle 2
Additional doses/cycles if infusion reactions
Hydrate: mL IV saline
Before carfilzomib; after (optional)
Monitor for over hydration
Administer carfilzomib IV
20 mg/m2 over 2-10 mins
Rinse IV with saline before and after
Carfilzomib AEs (All Grades) > 30%
Patients, %
Fatigue 56
Anemia 47
Nausea 45
Thrombocytopenia 36
Dyspnea 35
Diarrhea 33
Pyrexia 30
AE, adverse event; FDA, US Food and Drug Administration; IV, intravenous; PN, peripheral neuropathy.
The second of these agents, carfilzomib, was approved in July of It is the second proteasome inhibitor approved for the treatment of multiple myeloma. It is administered IV on 2 consecutive days for 3 consecutive weeks, followed by a week off, otherwise known as 21 out of 28 days. And carfilzomib has been associated with cardiopulmonary adverse events, and patients should be screened carefully prior to the administration and during treatment.
Monitor AEs, which may include cardiopulmonary
The drug may require dose adjustment for toxicities, diuretics, inhalers, minimal PN
Carfilzomib [package insert]. FDA.gov

45. Selected Problems Faced by Patients With MM and Their Caregivers
Information
Provide detailed information about AEs of medication
Adherence
Provide calendar with treatment regimen and dates of administration to improve adherence
Inform patient and caregiver of symptoms
DVT/PE, peripheral neuropathy, infection, bleeding, and neutropenia
Reinforce precautions
AE, adverse event; DVT, deep vein thrombosis; MM, multiple myeloma; PE, pulmonary embolism.
Living with multiple myeloma can be a daunting experience. Despite the improvement in survival for these patients, the diagnosis of multiple myeloma—similar to other cancers—is a life-changing event. Most patients will require frequent follow-up and intermittent treatment for the rest of their lives.
Wulff-Burchfield, et al. Bone Marrow Transplant. 2013;48: Fife BL, et al. Bone Marrow Transplant. 2009;43: Stenberg U, et al. Psychooncology. 2010;19:

46. Communication With Team Members
Communication with nursing staff
Improves quality of life
Reduces distress
Encourages active participation
Financial and social support
Treatment should NOT be compromised if patients lack financial or social support
Multidisciplinary cancer treatment team (social worker, dietary, etc)
Emphasize the importance of local and national support groups (transportation assistance, reimbursement)
Communication with the patient and their caregivers is essential to improving patient quality of life, improving adherence, and will promote active participation in self-management skills on the part of the patient and the caregiver. This will improve early identification and prompt management of adverse events, reducing the severity of these adverse events. Patients with multiple myeloma are often treated in a variety settings by a variety of providers. Communication among and between providers will promote a consistent message to the patients.
Given the expectations of lifelong follow-up and intermittent treatment, financial and social support is very important. Providing the patient with a list of resources, referring them to local, regional, and national or international support services will go a long way in helping them to live with multiple myeloma.
Bensing J, et al. Patient Educ Couns. 2013;90: Thorne S, et al. Patient Educ Couns. 2013;90: McMullen L. Semin Oncol Nurs. 2013;29:

47. Go Online for More CCO Coverage of Multiple Myeloma!
Capsule Summaries of all the key data, plus Expert Analysis panel discussions exploring the clinical implications Additional CME-certified slidesets on current myeloma treatment, with expert faculty commentary
You can go online for more CCO coverage of multiple myeloma at the information listed here. Thank you for joining us.
clinicaloptions.com/MyelomaNursing