Natural History of Relapsed MM After Initial Relapse

Conference Correspondent - TON - ASH 2015 - Multiple Myeloma, Conference Correspondent

The range of treatment options for patients with multiple myeloma (MM) has grown substantially in recent years, and many patients now receive combinations containing immunomodulatory drugs (IMiDs) and proteasome inhibitors as initial treatment. However, patients with MM invariably relapse after their initial treatment and require successive therapies to maintain disease control. Increased access to new therapies for treatment of relapsed disease has led to improved survival of patients with MM. However, the natural history of relapsed myeloma earlier in the course of relapsed disease has not been studied in detail. 

To more closely examine the natural history of relapsed MM earlier in the course of relapsed disease, researchers designed a global, multicenter, retrospective study to examine the current treatment approaches for initial relapses in MM and patient outcomes following application of successive treatment regimens. Patients with MM who experienced a first relapse between January 1, 2007, and December 31, 2011, were identified for inclusion in the study. Clinical and laboratory data were culled from medical records from the time of diagnosis through patients’ third relapse.

The study population included 315 patients, 59% of which were male. Median age at diagnosis was 59 years. An IMiD (thalidomide or lenalidomide), bortezomib, or alkylating agent (melphalan or cyclophosphamide) was part of the initial therapy in 63%, 36%, and 51% of patients, respectively. In addition, 93 (30%) patients had stem-cell transplantation as part of initial treatment. An IMiD (thalidomide, lenalidomide, or pomalidomide), proteasome inhibitor (bortezomib or carfilzomib), or alkylating agent (melphalan or cyclophosphamide) was part of the therapy for first relapse in 50%, 59%, and 33% of patients, respectively. The following table shows responses, as measured by the overall survival, progression-free survival, and time to next treatment for each line of therapy subsequent to the first date of treatment with an antimyeloma regimen for first disease relapse.

Treatment Outcomes After Initial Relapse (median months)
End Point Overall survival Progression-free survival Time to next treatment
2nd Line of Therapy (n = 307) 36.1 18.4 12.6
3rd Line of Therapy (n = 163) 13.4 8.3 6.4
4th Line of Therapy (n = 84) 15 9.8 6.6

This study clearly demonstrates the progressively shorter duration of disease control with each successive treatment regimen, reflecting concerns about cumulative drug resistance over time. Newer therapies have had a positive impact on overall survival from time of first relapse, but these results underscore the need for additional treatment options with novel mechanisms of action.

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Last modified: December 8, 2015