ONCOLOGY. Vol. 25 2

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Treatment-Related Adverse Events in Patients With Relapsed/Refractory Multiple Myeloma

By Ravi Vij, MD¹ | November 7, 2011

¹Washington University School of Medicine, St. Louis, Missouri

Other Toxicities

Tumor lysis syndrome

Fatal instances of tumor lysis syndrome (TLS) have not been reported during treatment of MM with lenalidomide. In clinical studies of bortezomib(Drug information on bortezomib) in R/R MM, several cases of TLS have been noted, with an incidence as high as 1.4% reported in one study.[64,65] There are no data currently available on the incidence of TLS related to treatment with pomalidomide. Two possible subclinical cases of TLS were observed during an early study of carfilzomib in patients with R/R MM.[38] With the implementation of prophylactic hydration guidelines, no further incidents have been observed.

Cardiopulmonary symptoms

In the APEX study, the incidence of heart failure events (acute pulmonary edema, cardiac failure, congestive cardiac failure, cardiogenic shock, pulmonary edema) was similar in the bortezomib (5%) and dexamethasone(Drug information on dexamethasone) groups (4%).[25] However, acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have been reported with bortezomib therapy, including reports in patients with no obvious risk factors.[66,67] There have also been isolated cases of QT-interval prolongation in clinical studies, although causality has not been established.[68]

There have been reports of acute diffuse infiltrative pulmonary disease of unknown etiology—such as pneumonitis, interstitial pneumonia, lung infiltration, or acute respiratory distress syndrome—in patients receiving bortezomib.[25] There have also been reports of pulmonary hypertension associated with bortezomib administration in the absence of left heart failure or significant pulmonary disease.[25] In the event of new or worsening cardiopulmonary symptoms, a prompt comprehensive diagnostic evaluation should be conducted.

CNS adverse effects

Seizures, including grand mal convulsions, have been reported during postapproval use of thalidomide(Drug information on thalidomide) in clinical practice.[69] The majority of patients had disorders potentially predisposing them to seizure activity.[42] There have been reports of reversible posterior leukoencephalopathy syndrome in patients receiving bortezomib.[70]

Hepatic events

There are a limited number of isolated case reports of severe hepatic toxicity secondary to treatment of MM patients with thalidomide and lenalidomide.[71,72] Cases of acute liver failure have been reported in patients receiving bortezomib with multiple concomitant medications and in those with serious underlying medical conditions. Other reported hepatic events include increases in liver enzymes, hyperbilirubinemia, and hepatitis.[25] Because bortezomib is metabolized via the liver, exposure is increased in patients with moderate or severe hepatic impairment.

Management

TABLE 8

Recommended Starting Dose Modification for Bortezomib (Velcade) in Patients With Hepatic Impairment

Patients at risk for tumor lysis should be monitored closely. Appropriate precautions should be taken, including adequate hydration and prophylactic administration of allopurinol(Drug information on allopurinol).[73] Management strategies should include modifications of doses and dosing schedules. Patients with moderate or severe hepatic impairment should start receiving bortezomib at a reduced dose of 0.7 mg/m2 per injection during the first cycle, with subsequent dose adjustments based on patient tolerance (Table 8).[25]

Conclusions

Lenalidomide-, thalidomide-, and bortezomib-based therapies all have predictable but differing toxicity profiles.[3] Most AEs are manageable with dose reduction or interruption,[3,6], and prophylactic and supportive care is an essential part of R/R MM therapy.[6,74,75] However, newer agents such as pomalidomide and carfilzomib, with improved safety profiles would be invaluable for patients with R/R MM.[23]

Acknowledgments: The authors would like to thank Joanne Dalton, BSc, and Brian E. Szente, PhD, of Fishawack Communications for their assistance with manuscript development. Editorial support was funded by Onyx Pharmaceuticals.

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SUPPLEMENT

The Future of Treatment for Patients With Relapsed/ Refractory Multiple Myeloma

The goal of this supplement is to present a comprehensive overview of the major current and emerging treatment options for patients with relapsed and/or refractory multiple myeloma.

The Future of Treatment for Patients With Relapsed/Refractory Multiple Myeloma
ONCOLOGY, November 7, 2011

Multiple Myeloma: A Clinical Overview
ONCOLOGY, November 7, 2011

Current Challenges in the Management of Patients with Relapsed/Refractory Multiple Myeloma
ONCOLOGY, November 7, 2011

Comparative Mechanisms of Action of Proteasome Inhibitors
ONCOLOGY, November 7, 2011

Current Advances in Novel Proteasome Inhibitor–Based Approaches to the Treatment of Relapsed/Refractory Multiple Myeloma
ONCOLOGY, November 7, 2011

Current Advances in Non–Proteasome Inhibitor–Based Approaches to the Treatment of Relapsed/Refractory Multiple Myeloma
ONCOLOGY, November 7, 2011

Treatment-Related Adverse Events in Patients With Relapsed/Refractory Multiple Myeloma
ONCOLOGY, November 7, 2011

The Future of Proteasome Inhibitors in Relapsed/Refractory Multiple Myeloma
ONCOLOGY, November 7, 2011

Topic Index

Cancer Types
Breast Breast (HER2+) Breast (Triple-Negative) CML Colorectal Gastrointestinal GIST Genitourinary Gynecologic Head & Neck	Hematology Kidney (Renal Cell) Leukemia Lung Lymphoma Melanoma Multiple Myeloma Ovarian Prostate Sarcoma
Supportive Care	More Topics
Bone Metastases End-of-Life Care Palliative Care	Ethics in Oncology Practice Management Practice & Policy

All Topics