Outcomes of primary refractory multiple myeloma and the impact of novel therapies.

Abstract

Over the past decade, use of novel agents, including immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) has resulted in high response rates and improvement in overall survival (OS) for patients with multiple myeloma (MM); however, the prognostic significance of refractoriness to these agents when used as initial therapy has not been extensively studied. We reviewed the outcomes of 816 consecutive patients treated for MM at our institution since 2006 to evaluate the survival difference between those achieving at least a partial response (PR) to induction therapy and those who were primary refractory. The median OS from start of therapy was significantly shorter for the primary refractory group at 3.6 vs. 7.6 years for the responding patients (P < 0.001). The difference in median OS persisted when only patients receiving a novel agent as part of induction therapy were considered (3.6 vs. 7.9 years, P < 0.001) and in a 4-month landmark analysis (4.2 vs. 7.6 years, P < 0.001). The median OS for patients achieving a complete response (CR), very good partial response (VGPR), PR, or less than PR was not reached (NR), 6.1, 6.4, and 4.2 years from the 4-month landmark, respectively (P < 0.001). The comparatively poor outcomes of patients refractory to induction therapy in the current era of novel agents suggests that this high-risk subpopulation must be further studied for predictors of resistance and, when identified, should be targeted for clinical trials.

• Authors: Neil Majithia, S Vincent Rajkumar, Martha Q Lacy, Francis K Buadi, Angela Dispenzieri, Morie A Gertz, Suzanne R Hayman, David Dingli, Prashant Kapoor, Lisa Hwa, John A Lust, Stephen J Russell, Ronald S Go, Robert A Kyle, Shaji K Kumar
• Journal: American journal of hematology (Am J Hematol) Vol. 90 Issue 11 Pg. 981-5 (Nov 2015) ISSN: 1096-8652 [Electronic] United States
• PMID: 26214732 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Immunologic Factors
• Proteasome Inhibitors
• Thalidomide
• Bortezomib
• Doxorubicin
• Cyclophosphamide
• Lenalidomide
• Melphalan
• Prednisone

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols
• Bortezomib (therapeutic use)
• Cyclophosphamide (therapeutic use)
• Doxorubicin (therapeutic use)
• Female
• Humans
• Immunologic Factors (therapeutic use)
• Lenalidomide
• Male
• Melphalan (therapeutic use)
• Middle Aged
• Multiple Myeloma (diagnosis, diagnostic imaging, drug therapy, mortality)
• Prednisone (therapeutic use)
• Proportional Hazards Models
• Proteasome Inhibitors (therapeutic use)
• Radiography
• Recurrence
• Remission Induction
• Retrospective Studies
• Survival Analysis
• Thalidomide (analogs & derivatives, therapeutic use)
• Treatment Outcome