Supplement December 2014 VOL 5, NO 6

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Establishing and Managing Expectations for Length of Therapy in Multiple Myeloma

Multiple Myeloma Nurse Roundtable Saturday, October 5, 2013
Boston, Massachusetts

The roundtable was supported by Takeda, and was comprised of oncology nurses, advanced practitioners, and oncology nurse navigators. The purpose of the roundtable was to gain insight on nurse and patient educational needs as well as management of patients during therapy. Participants were asked to provide insight on their experience as it related to managing and navigating patients with multiple myeloma, more specifically their feedback on:

• Managing the length of therapy
• Appropriate treatment options and side effects
• Challenges of staying on therapy
• Best practices to assess and manage side effects.

Participants
Beth Faiman, PhD(c), MSN, APRN-BC, AOCN – Moderator
Cleveland Clinic Taussig
Cancer Institute
Cleveland, Ohio

Joseph D. Tariman, PhD, APRN, BC – Faculty
Northwestern University
Myeloma Program
Chicago, Illinois

Jessica Bailey, RN, BSN, OCN
Hematology Oncology Clinic
Baton Rouge, Louisiana

Eileen Bannon, RN, MSN, OCN, CBCN
Hershey Medical Center
Penn State Cancer Institute
Hershey, Pennsylvania

Kristin Barber, APRN
Utah Cancer Specialists
Salt Lake City, Utah

Deborah Christensen, RN, AHNB-BC
Dixie Regional Medical Center
St. George, Utah

Kathleen Clifford, RN, MSN, FNP-BC, AOCNP, ACHPN
St. Luke’s Mountain States
Tumor Institute
Boise, Idaho

Penny Daugherty, RN, MS, OCN
Northside Hospital
Atlanta, Georgia

Seth Eisenberg, RN, OCN
Seattle Cancer Care Alliance
Seattle, Washington

Paula Falzone, RN, BSN
Mt. Auburn Hospital-Oncology Hematology Clinic
Cambridge, Massachusetts

Gennie Howe, BSRN
North Texas Regional Cancer Center
Plano, Texas

Connie Kinney, RN, BSN, OCN
UPMC Cancer Centers-Hillman Cancer Center
Pittsburgh, Pennsylvania

Margaret Rummel, RN, BSN, OCN, MHA
Abramson Cancer Center
Philadelphia, Pennsylvania

Barbara Watson, RN, MSN, OCN
Community Health Network
Indianapolis, Indiana

Multiple myeloma (MM) is a relatively uncommon type of cancer. It is a malignancy of plasma cells that accumulate in bone marrow,leading to bone destruction and marrow failure.1 In the United States, about 24,050 new cases were expected to be diagnosed in 2014, and about 11,090 deaths were expected to occur.2 MM incidence increases with advancing age.3 There is a higher incidence of MM in males than in females, and in black Americans than in white Americans.3 Although MM remains incurable, survival is improving.4

Pathophysiology of Multiple Myeloma
Normally, plasma cells produce various types of immunoglobulin (Ig) as part of an immune response.2,5 In MM, neoplastic plasma cells accumulate in the bone marrow and produce a single clone of an Ig known as M protein, or paraprotein.2,5,6 MM is characterized by uncontrolled proliferation of these abnormal plasma cells (ie, myeloma cells) and, in most cases, excess M protein, which can be used to diagnose MM.2,5,6 Myeloma cells can interact with and adhere to bone marrow stromal cells, which leads to adhesion-and cytokine-mediated signaling. Cytokines, such as interleukin-6, may mediate tumor cell growth and survival.5,6 In addition to M protein, malignant plasma cells produce varying amounts of monoclonal free light chains (components of M protein). Light chains in the urine, referred to as Bence Jones proteins, are sometimes detected in laboratory studies of patients with myeloma. Among patients who have MM, approximately 20% produce only light chains in the serum and urine, and 2% produce neither light chains nor a paraprotein (non-secretors).2,5,6

Several types of M protein, most commonly IgG and IgA, are observed in patients with MM1,2,6; the subtypes of MM are based on the type of M protein secreted. The most common subtype of MM, with 70% of cases, is IgG; approximately 20% of cases are IgA. Approximately 15% of patients with IgG myeloma have coagulation-related complications, compared with ˃33% of patients with IgA myeloma. IgA myeloma may be associated with poor prognosis despite higher initial response to therapy, compared with other MM subtypes.5

dec2014supplementtable1

Clinical Features
As shown in Table 1, MM symptoms and their common causes vary widely depending on the underlying pathophysiology.5 Anemia, bone fractures, hypercalcemia, and renal impairment are all relatively common in patients with MM.2 High levels of M protein (or monoclonal gammopathy) can cause symptoms of hyperviscosity (headaches, nosebleed, blurred vision, and confusion),6 while reduction in the normal immune response can mean recurrent bacterial infections.2,6 Acute renal failure, cord compression, and hypercalcemia are true medical emergencies. Prompt diagnosis and treatment are vital to minimize long-term organ damage from these complications of MM.6

Diagnostic Criteria and Staging
According to the National Comprehensive Cancer Network, patients suspected of having MM should have a history and physical examination as well as blood, serum, urine, and biologic assessments.1 Laboratory blood assessments include testing for beta2 microglobulin (ß2M), which is used to measure the tumor burden.1 Urine analyses include evaluating 24-hour urine for total protein, urine protein electrophoresis, and urine immunofixation electrophoresis.1 Serum analyses include testing for Ig (IgG, IgA, and IgM) levels, serum protein electrophoresis, and serum immunofixation electrophoresis.1 Both serum and urine analyses are used to test for M protein and component light chains.1,5

In addition to laboratory testing, chromosome analysis is normally conducted to identify cytogenetic abnormalities in MM. Chromosomal deletions, translocations, and amplifications detected by fluorescence in situ hybridization or conventional cytogenetics are common in patients with MM.1,7,8 High-risk chromosomal aberrations are characterized by 17p deletion, t(14;16) and t(14;20) translocations, and a high-risk gene expression profiling signature. Other abnormalities are typically characterized as standard or intermediate risk.1,7-10

In patients with monoclonal gammopathy of undetermined significance, a number of criteria are used to establish a diagnosis of symptomatic MM, including M protein in the serum or urine (required), bone marrow clonal plasma cells ≥10% or documented plasmacytoma (required), and related organ and tissue impairment, as measured by “CRAB” criteria (≥1 required)1,6,11:
• Hypercalcemia: serum calcium >11.5 mg/dL
• Renal dysfunction: serum creatinine >2 mg/dL
• Anemia: hemoglobin <10 g/dL or 2 g/dL below lower limit of normal • Bone disease (osteolytic lesions or osteopenia). Treatment of symptomatic MM may depend on patient age and comorbidities.1,6 For patients with symptomatic MM, the International Staging System defines 3 risk categories based on serum concentrations of ß2M and albumin.12

Stage I is characterized by serum ß2M less than 3.5 mg/L plus serum albumin at least 3.5 g/dL, and stage III by serum ß2M at least 5.5 mg/L (without regard to serum albumin level). Stage II is identified in either of 2 ways: serum ß2M less than 3.5 mg/L plus serum albumin less than 3.5 g/dL or serum ˃2M greater than 3.5 mg/L but less than 5.5 mg/L (without regard to serum albumin level).12

Treatment of Multiple Myeloma with Velcade
Velcade (bortezomib) is indicated for the treatment of patients with MM. Bortezomib is indicated for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy.13

Bortezomib is contraindicated in patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol. Reactions have included anaphylactic reactions. Bortezomib is contraindicated for intrathecal administration. Fatal events have occurred with intrathecal administration of bortezomib.13

Efficacy Data
Bortezomib was studied in the Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment with Melphalan and Prednisone (VISTA) trial, a randomized, open-label, international trial evaluating the efficacy and safety of bortezomib plus melphalan/ prednisone (Bortezomib + MP) versus melphalan/prednisone (MP) in previously untreated patients with MM who were ineligible for high-dose therapy plus autologous stem cell transplantation. The primary end point for the study was time to progression and secondary end points included complete response, overall response rate, progression-free survival, and overall survival.14

In the VISTA trial, 682 patients were randomized to bortezomib + MP (n=344) or MP (338). In the bortezomib + MP arm, bortezomib was administered in combination with oral melphalan and oral prednisone for nine 6-week treatment cycles. In cycles 1 through 4 (total of 24 weeks), bortezomib (1.3 mg/m2) was administered by intravenous (IV) bolus twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32, and melphalan (9 mg/m2) and prednisone (60 mg/m2) were administered on days 1 to 4 of each cycle. In cycles 5 through 9 (total of 30 weeks), bortezomib (1.3 mg/m2) was administered once weekly on days 1, 8, 22, and 29, and melphalan (9 mg/m2) and prednisone (60 mg/m2) were administered on days 1 to 4 of each cycle. In the MP arm of the study, melphalan (9 mg/m2) and prednisone (60 mg/m2) were administered on days 1 to 4, every 6 weeks, for a total of 54 weeks (Figure 1).14

dec2014supplementfigure1

The MP arm crossed the median at the 36.7 months median follow-up analysis and it was not until the 60.1 months median follow-up analysis that overall survival was defined for both arms. Likewise, bortezomib combination therapy delivered significantly higher complete response and overall response rate in the bortezomib + MP arm versus the MP arm, as measured by the European Group for Blood and Marrow Transplantation criteria13-15—a standard for complete response.16 Further enrollment was halted, and patients receiving MP alone were offered bortezomib in addition.13,14 Response rates are shown in Figure 2.

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At a later pre-specified analysis with a 3-year median follow-up, bortezomib + MP provided an overall survival advantage over MP that was not regained with subsequent therapies.13 Of the 69% of MP patients who received subsequent therapies, 50% received bortezomib or a bortezomib-containing regimen.17

After median follow up of 60.1 months, there was a 31% reduced risk of death following treatment with VELCADE MP versus MP (HR 0.695; P <.001).18 Bortezomib-based therapy delivered a statistically significant 13.3-month overall survival advantage over MP (P <.05); median overall survival was 56.4 months for bortezomib + MP versus 43.1 months for MP alone (Figure 3). These were achieved with a median of 50 weeks of treatment.13

dec2014supplementfigure3

With bortezomib + MP, responses deepened with continued treatment through 54 weeks and beyond completion of therapy, and 28% of complete responses were achieved after 24 weeks of therapy. Furthermore, at the end of the planned duration of therapy (54 weeks), 102 patients (30% of the evaluable population) had achieved a complete response and 136 patients (40% of the evaluable population) had achieved a partial response (refer to Figure 4, on page 8).19

dec2014supplementfigure4

Bortezomib dosing schedule for previously untreated patients with MM
The recommended dose of bortezomib is 1.3 mg/ m2 administered in combination with melphalan (9 mg/m2) plus prednisone (60 mg/m2).13
• Twice weekly (cycles 1-4): Bortezomib should be administered on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 6-week cycle, and MP should be administered on days 1 through 4 every cycle for a total of 24 weeks
• Weekly (cycles 5-9): Bortezomib should be administered on days 1, 8, 22, and 29 of a 6-week cycle, and MP on days 1 through 4 every cycle for a total of 30 weeks
Bortezomib can be administered subcutaneously or as a 3-to 5-second bolus IV injection. At least 72 hours should elapse between consecutive doses of bortezomib.13 There are treatment calendars available to help patients stay on track with their bortezomib therapy.
In the VISTA trial, rates of discontinuation as a result of treatment-related adverse reactions (ARs) were 11% for bortezomib combination and 10% for MP alone.14 Prior to initiating any cycle of therapy with bortezomib in combination with MP, platelet count should be at least 70 × 109/L and absolute neutrophil count should be at least 1.0 × 109/L.13 Dosing adjustments of bortezomib are not necessary for patients with renal insufficiency. In patients undergoing dialysis, bortezomib should be administered after the dialysis procedure.13 Dose modifications may be necessary for hematologic toxicities, nonhematologic toxicities, peripheral neuropathy (PN), and moderate to severe hepatic impairment.13

Safety Data
Patients participating in the VISTA trial experienced hematologic and nonhematologic ARs. With bortezomib + MP, the most commonly reported (≥20%) treatment-related ARs included thrombocytopenia (48% vs 42% with MP), neutropenia (47% vs 42% with MP), anemia (32% vs 46% with MP), leukopenia (32% vs 28% with MP), lymphopenia (23% vs 15% with MP), nausea (39% vs 21% with MP), diarrhea (35% vs 6% with MP), vomiting (26% vs 12% with MP), constipation (23% vs 4% with MP), peripheral neuropathy (PN) (46% vs 1% with MP), neuralgia (34% vs <1% with MP), and fatigue (25% vs 14% with MP).13

With regard to hematologic toxicities, complete blood count should be monitored regularly throughout treatment. Prior to initiating any cycle of therapy with bortezomib + MP, platelet count should be at least 70 × 109/L and the absolute neutrophil count should be at least 1.0 × 109/L.13

Likewise, patients should be monitored for nonhematologic toxicities, including hepatic impairment. Cases of acute liver failure have been reported, in addition to other hepatic events such as elevated liver enzymes, hyperbilirubinemia, and hepatitis. Prior to initiating any cycle of therapy with bortezomib + MP, nonhematologic toxicities (except PN) should have resolved to grade 1 or baseline.13

Refer to Section 2 of the full bortezomib Prescribing Information for specific dose modification guidelines for hematologic and nonhematologic toxicities.

As shown in Table 2, in the VISTA trial, the incidence of new-onset ARs was lower after week 24 of bortezomib-based therapy. Results were achieved with bortezomib + MP twice weekly followed by once-weekly administration. The incidence of new-on-set ARs was defined as the number of patients having a new onset of an event within weeks 1 to 24 and weeks 25 to 54.15 Rates of discontinuation because of ARs were 11% with bortezomib + MP and 10% with MP alone.15 Among patients in the VISTA trial treated with bortezomib + MP, 36% had 1 dose reduction during the study and 18% required 2 dose reductions.15

dec2014supplementtable2

A total of 25% of patients in the treatment group receiving bortezomib + MP experienced serious ARs versus 18% of patients in the treatment group receiving MP. The most commonly reported serious ARs with bortezomib + MP versus MP alone included pneumonia (5% vs 4%), diarrhea (4% vs 0%), thrombocytopenia (3% vs 1%), vomiting (3% vs <1%), nausea (2% vs <1%), anemia (2% vs 2%), herpes zoster (2% vs <1%), and dehydration (2% vs <1%).15

In patients treated with bortezomib + MP, 47% experienced treatment-emergent PN, including 13% with grade ≥3. Eleven percent of patients discontinued treatment with bortezomib because of PN and continued MP; 3% of patients discontinued treatment with bortezomib + MP because of PN.20 However, onset of PN plateaued after approximately 24 weeks of planned therapy (as measured by cumulative bortezomib dose to first onset of PN)—Figure 5.20

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Oncology nurses and other clinicians should be aware that PN may be manageable and reversible with appropriate dose modification, including discontinuation. In a subanalysis of the phase 3 VISTA trial data, 79% of patients experienced improvement by at least 1 grade, using the National Cancer Institute Common Terminology Criteria for Adverse Events, within a median of 1.9 months. Furthermore, 60% of patients experienced complete resolution within a median of 5.7 months (Figure 6).20

dec2014supplementfigure6

Complete resolution was defined as a return to PN baseline in those patients with preexisting grade 1 PN and a complete absence of PN in all other patients.20 As shown in Table 3, guidelines for dose modification for PN vary by the severity of PN signs/symptoms.

dec2014supplementtable3

No drugs are specifically approved for the treatment of PN seen with MM, but recommendations across the grades may include healthy habits to maintain optimal weight and nutritional status, correcting any vitamin deficiencies, physical therapy, and pain management.21,22

Efficacy and Safety of Subcutaneous Bortezomib
In 2012, bortezomib received US Food and Drug Administration approval for subcutaneous (SC) administration.13 A randomized, phase 3, noninferiority study was conducted to evaluate SC versus IV administration of bortezomib in patients with relapsed MM. A total of 222 patients were randomly assigned to receive up to eight 21-day cycles of bortezomib 1.3 mg/m2 via SC (n=148) or IV (n=74) routes of administration. Patients received a median of 8 cycles (range 1 - 10) in both groups.23

In the study, overall response rate at 12 weeks was 43% with SC bortezomib versus 42% with IV bortezomib. The study met its primary noninferiority objective that single-agent SC bortezomib retained at least 60% of the overall response rate after 4 cycles relative to single-agent IV bortezomib.13

With bortezomib, PN incidence varies by route of administration (Figure 7). In relapsed MM, a total of 37% of patients receiving SC bortezomib experienced PN (6% grade ≥3), compared with 50% of patients receiving IV bortezomib (15% grade ≥3). Starting patients subcutaneously may be considered for patients with preexisting PN or patients at high risk for PN. The dosing schedule of bortezomib is the same for IV and SC routes of administration; however, the reconstitution volumes and final concentrations for administration differ.13

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Subcutaneous Administration of Bortezomib
SC bortezomib should be administered in a manner consistent with best practices and good nursing principles, which include the following:24
• For all SC injections, maintain aseptic procedures
• Nurses should wash their hands before giving the injection and following the administration of bortezomib
• Gloves should be worn; however, they may not rotect from needlestick injuries
• Sharps should be carefully and immediately disposed of at the point of administration.

The abdomen or thighs are the recommended sites for SC administration of bortezomib (Figure 8). Injection sites should be rotated. New injections should be administered at least 1 inch from an old site and never into areas where the skin is tender, bruised, erythematous, or indurated.13

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Before administration, ensure that the needle used during preparation has been changed to a new, clean, sharp, dry needle.25 This practice may reduce the chance of topical contact of medication with the skin, which may cause injection-site reactions. In addition, make sure there is adequate adipose tissue at the site of injection.25,26

Ensure medication is deposited in the SC tissue, as shown in Figure 9.26 Generally, when using a 25-gauge needle that is 5/8 inch in length, insert the needle at a 45-degree angle.26,27 When using a 26- to 30-gauge needle that is 1/2 inch in length, insert the needle at a 90-degree angle.26,27 Inject slowly and steadily, over several seconds,25 to allow absorption into SC tissue; pause briefly before withdrawing the needle to avoid backtracking of the fluid and absorption into the skin.24

dec2014supplementfigure9

As with IV injections, it is important to educate patients and their families about the ARs that patients may experience with SC injections.24 If local injection-site reactions occur following administration of bortezomib subcutaneously, a less concentrated bortezomib solution (1 mg/mL instead of 2.5 mg/mL) may be administered subcutaneously. Alternatively, consider the IV route of administration.13

For more information, please see Administration Precautions, section 2.7, in the full Prescribing Information.

Patient Management Considerations with Bortezomib
The Oncology Nurse Roundtable was convened to bring together oncology nurses, advanced practitioners, and oncology nurse navigators to discuss the use of bortezomib in the treatment of MM, describe the challenges of keeping patients on bortezomib therapy, and allow participants to share best practices in managing ARs and ensuring that appropriate length of therapy is reached. This highly interactive program included several case studies to stimulate dialogue and exchange of ideas among the participants. The following section highlights the key discussion points and insights from the meeting.

Addressing Patient Needs
Nurses, advanced practitioners, and nurse navigators play a critical role in the care of patients with MM. Similar to many other cancers, the number of treatment options for MM has grown in recent years.4

Roundtable participants identified a number of considerations to help guide interaction with new patients and foster good communication throughout the treatment process, including28:
• Establishing rapport as quickly as possible
• Being a good listener and allowing patients to ask as
many questions as possible
• If appropriate, bringing family members and/or caregivers into treatment discussions early in the process
• Recognizing that each patient is different; therefore, education should be individualized as much as possible
• Understanding that patients are often overwhelmed by their diagnosis; therefore, ongoing education and reinforcement of key educational messages is crucial to ensuring that patients understand their treatment plan.

“Our practice has an education program where new patients meet with the nurse navigator. We try to create a supportive environment, where patients feel comfortable asking as many questions as they need to, and we spend as much time with them as we can.”
- Deborah Christensen, RN, AHNB-BC

Oncology nurses and other clinicians should be aware that their patients may face nonclinical barriers to treatment such as cost of treatment and access to therapy. In particular, travel restrictions were singled out by a number of participants as a limiting factor for patients requiring frequent appointments. Travel issues may sometimes affect dosing schedules for anticancer agents. To address this issue, some practices have made an effort to “bundle” chemotherapy treatment and ancillary care appointments. It was also noted that some institutions offer free or subsidized transportation services for patients in need.

In addition to recognizing and addressing nonclinical barriers to treatment, it is critical to begin educating patients about MM and their treatment regimen as soon as possible, preferably before therapy is initiated. According to several participants, education is best accomplished using a holistic, coordinated approach, involving both clinical and nonclinical aspects of treatment. These efforts may include nurses, advanced practitioners, physicians, pharmacists, dietitians, nurse navigators, and financial counselors.

Setting Expectations Regarding Treatment
As with other anticancer agents, it is important for oncology nurses and other clinicians to appropriately manage patients receiving bortezomib-containing regimens. Management considerations may include (but not be limited to) dosing, administration, management of toxicities, and adherence to treatment.

As part of the treatment education process, participants voiced the need to set patient expectations about length of therapy. In the VISTA trial, responses deepened over time with longer bortezomib combination (bortezomib + MP) therapy, and after 16.3 months, 69% of evaluable patients in the intent-to-treat group had achieved either a complete or a partial response.19 This information resonated with the roundtable panel, and many participants indicated that they strongly encourage their patients with previously untreated MM to remain on bortezomib therapy as long as possible (up to 54 weeks as seen in the VISTA trial). Nevertheless, practices may encounter challenges if patients want a “break” from bortezomib treatment. In this case, it is important to remind patients that uninterrupted treatment (in accordance with labeled dosing) provides patients with the best opportunity to achieve the therapeutic benefit seen in the clinical trial.

“We tell patients that they’re going to be on (Bortezomib) therapy for quite a while. Our physicians will usually administer 8 cycles and then reevaluate. For patients responding to treatment, we’ll continue therapy with the goal of one year of therapy.”
- Paula Falzone, RN, BSN

Participants indicated that frequent patient follow-up, practice accessibility during nonbusiness hours, and ongoing patient education were all helpful in supporting treatment adherence. When appointments are missed, participating practices typically call the patient the same day to check on them and try to schedule another appointment.

“Patient education is an ongoing process. It’s very important to build that rapport with the patient and then keep them engaged throughout the treatment process.”
- Eileen Bannon, RN, MSN, OCN, CBCN

Management of Treatment-Related ARs with Bortezomib
Some patients on bortezomib-containing regimens may experience treatment-related ARs. Prior to treatment initiation, participants indicated that they try to educate their patients about the possibility of ARs. According to the participants, informing patients in advance often serves to reduce anxiety, especially in the early stages of treatment.28

When treatment-related ARs occur, they should be identified, assessed, and reported as soon as possible. Patients may experience fatigue, gastrointestinal issues, and other symptoms, but oncology nurses, advanced practitioners, and nurse navigators are often the first to identify these symptoms as ARs during their interactions with patients. Other ARs, such as myelosuppression, may be identified through laboratory work.

PN is a common AR of bortezomib.13 Starting bortezomib subcutaneously may be considered for patients with preexisting PN or at high risk for PN.

When monitoring for PN, several participants noted that it is important to recognize that symptoms may vary.
“Sometimes nurses focus on the tingling and numbness, but there may be other symptoms such as pain, weakness, or difficulty walking.29 Those are suggestive of neuropathy as well, and we make sure that we ask questions about those symptoms.
- Seth Eisenberg, RN, OCN

PN may be identified through the use of validated assessment tools, such as the 11-item Neurotoxicity Assessment Tool adapted from the National Cancer Institute Common Terminology Criteria for Adverse Events.29 However, many participants indicated that they use less formal techniques to detect loss of sensation, such as asking the patient to pick up a paper clip or button a shirt in their presence. Sometimes patients may not be aware that they are experiencing PN (or other ARs). Therefore, it may be helpful for the nurse to investigate whether patients may be altering their normal habits because of treatment-related symptoms. In some cases, family members and caregivers may be instrumental in helping nurses and other clinicians to identify PN and other treatment-related ARs.

In a clinical trial with bortezomib-based therapy, the incidence of new-onset ARs was highest in the first 24 weeks of treatment.15 Participants indicated that patients are typically monitored very closely early in the course of therapy, especially for the first few cycles of treatment. Patients experiencing new or worsening PN during therapy with bortezomib may require a decrease in the dose, a less dose-intense schedule, or discontinuation. For these patients, there are specific guidelines that depend on the severity of signs and symptoms (refer to Table 3, page 10). In general, participants indicated that they were aware of these guide-lines and used them when appropriate.

Bortezomib can be administered through SC and IV routes of administration. Because there is a difference in the incidence of PN by route of administration in patients with MM, practices may consider starting bortezomib subcutaneously for patients with preexisting PN or patients at high risk for PN.

When treatment-related ARs develop, they are assessed by the clinical team and, in consultation with the patient and/or family/caregiver, a path of action is agreed upon. Depending on severity, some ARs may necessitate dose modification or discontinuation. Please see full prescribing information at http://www.velcade.com/Files/PDFs/ VELCADE_PRESCRIBING_INFORMATION.pdf for dosing modification information with hematologic toxicities, nonhematologic toxicities, peripheral neuropathy, and moderate to severe hepatic impairment.

Supportive and Prophylactic Care
In randomized studies in previously untreated and relapsed MM, herpes zoster reactivation was more common in subjects treated with bortezomib (range, 6%-11%) than in the control groups (3%-4%). Therefore, antiviral prophylaxis should be considered in patients being treated with bortezomib.13

Conclusion
In summary, the roundtable panel was comprised of a knowledgeable, experienced group of oncology nurses, advanced practitioners, and oncology nurse navigators who were well versed in managing anticancer therapies in general and bortezomib in particular. Participants emphasized a number of key points for helping patients through treatment:
• Begin speaking with patients about their anticancer treatment regimen as soon as possible. Build rapport to foster good communication throughout the treatment period
• Encourage patients to include family members and/ or caregivers in the process early and maintain open dialogue throughout the treatment process
• Identify and seek to address any nonclinical impediments to treatment such as cost, travel issues, or cultural barriers. Be aware that these issues may impact adherence to therapy if they are not addressed
• Set treatment expectations early. Let patients know that treatment of MM is typically long term. Patients receiving bortezomib for previously untreated MM should expect treatment for up to 54 weeks
• Be realistic about potential ARs such as PN and fatigue. Reinforce the importance of reporting ARs when they occur.
Roundtable participants agreed that following these eneral guidelines could contribute to a positive treatment experience for patients with MM, including those receiving bortezomib.

Support services, including financial, treatment, and personal assistance and resources, are available to patients with MM who are receiving bortezomib.

References

1. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Multiple Myeloma; Version 2.2014. © 2013 National Comprehensive Cancer Network, Inc. www.nccn.org/profession als/physician_gls/f_guidelines.asp#site. Accessed January 21, 2014.
2. American Cancer Society. Multiple Myeloma Overview Guide. © 2013 American Cancer Society Web site http://www.cancer.org/cancer/multiplemyeloma/over viewguide/index. Updated February 13, 2013. Accessed January 30, 2014.
3. Waxman AJ, Mink PJ, Devesa SS, et al. Racial disparities in incidence and outcome in multiple myeloma: a population-based study [published online ahead of print September 7, 2010]. Blood. 2011;116:5501-5506.
4. Bergsagel PL, Mateos M-V, Gutierrez NC, Rajkumar SV, San Miguel JF. Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multi- ple myeloma [published online ahead of print November 19, 2012]. Blood. 2013;121:884-892. 5. Munshi NC, Anderson KC. Plasma cell neoplasms. In: DeVita VT Jr, Lawrence TS, Rosenberg SA. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011:1997-2032.
6. Smith D, Yong K. Multiple myeloma. BMJ. 2013;346:f3863.
7. Walker BA, Leone PE, Chiecchio L, et al. A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value. Blood. 2010;116:e56-e65.
8. Rajkumar SV. Multiple myeloma: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol. 2012;87:78-88.
9. Drach J, Schuster J, Nowotny H, et al. Multiple myeloma: high incidence of chromosomal aneuploidy as detected by fluorescence in situ hybridization. Cancer Res. 1995;55:3854-3859.
10. Kumar SK, Mikhael JR, Buadi FK, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo stratification of myeloma and risk-adapted therapy (mSMART) consensus guidelines. Mayo Clin Proc. 2009;84:1095-1110.
11. Durie BGM, Harousseau J-L, Miguel JS, et al; for the International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467-1473.
12. Greipp PR, San Miguel J, Durie BGM, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412-3420.
13. VELCADE [prescribing information]. Cambridge, MA: Millennium Pharmaceuticals, Inc; 2014.
14. San Miguel JF, Schlag R, Khuageva NK, et al; for the VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for the initial treatment of multiple myeloma. N Engl J Med. 2008;359:906-917.
15. Data on file 42, 48, 53, 59, 60, 61. Millennium Pharmaceuticals, Inc.
16. Bladé J, Samson D, Reece D, et al; for the Myeloma Subcommittee of the EBMT (European Group for Blood and Marrow Transplantation) Chronic Leukaemia Working Party and the Myeloma Working Committee of the IBMTR (International Bone Marrow Transplant Registry) and ABMTR (Autologous Blood and Marrow Transplant Registry). Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Br J Haematol. 1998;102:1115-1123.
17. Mateos M-V, Richardson PG, Schlag R, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010;28:2259-2266.
18. San Miguel JF, Schlag R, Khuageva NK, et al. Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol. 2013;31:448-455.
19. Harousseau J-L, Palumbo A, Richardson PG, et al. Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone. Blood. 2010;116:3743-3750.
20. Dimopoulos MA, Mateos M-V, Richardson PG, et al. Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study. Eur J Haematol. 2010;86:23-31.
21. National Institute of Neurological Disorders and Stroke. Peripheral Neuropathy Fact Sheet. NIH Publication No. 04-4853. www.ninds.nih.gov/disorders/peripher alneuropathy/ detail_peripheralneuropathy.htm#115863208. Accessed January 28, 2014.
22. Tariman JD, Love G, McCullagh E, Sandifer S; and IMF Nurse Leadership Board. Peripheral neuropathy associated with novel therapies in patients with multiple myeloma: consensus statement of the IMF Nurse Leadership Board. Clin J Oncol Nurs. 2008;12(3 suppl):29-35.
23. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, noninferiority study. Lancet Oncol. 2011;12:431-440.
24. Hunter J. Subcutaneous injection technique. Nurs Stand. 2008;22:41-44.
25. Ostendorf W. Administration of parenteral medications. In: Perry AG, Potter PA, Elkin MK. Nursing Interventions and Clinical Skills. 5th ed. St Louis, MO: Elsevier Mosby; 2012:541-583.
26. Smith SF. Parenteral medication administration. In: Smith SF, Duell DJ, Martin BC. Clinical Nursing Skills Basic to Advanced Skills. 8th ed. Upper Saddle River, NJ: Pearson Education, Inc; 2012:607-630.
27. Workman B. Safe injection techniques. Nurs Stand. 1999;13:47-53.
28. Epstein RM, Street RL Jr. Patient-Centered Communication in Cancer Care: Promoting Healing and Reducing Suffering. National Cancer Institute, NIH publication 07-6225. Bethesda, MD, 2007. http://appliedresearch.cancer.gov/areas/pcc/communication/monograph.html. Accessed January 28, 2014.
29. Neurotoxicity Assessment Tool. Millennium Pharmaceuticals, Inc. 2012
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