With more novel agents available for the treatment of multiple myeloma, including immunomodulators and proteasome inhibitors, response rates and overall survival have improved in this patient population. However, there is little information about the consequences of refractoriness to these agents when used as initial therapy.
A recent study conducted by Neil Majithia, MD, from Mayo Clinic in Rochester, Minnesota, and colleagues found that patients who do not respond to induction therapy have poorer outcomes than those who achieve a partial response or better on these novel agents.
"Despite improved treatment options and new drugs, there is a small proportion of patients who can be refractory to these drugs, and the outcome of these patients is poor," Shaji K. Kumar, MD, also from Mayo Clinic and corresponding author of the study, told ASH Clinical News. "These patients should be encouraged to participate in clinical trials that explore novel approaches."
In the study, published in the American Journal of Hematology, the researchers reviewed outcomes of 816 consecutive patients treated for multiple myeloma at the Mayo Clinic in Rochester, Minnesota, since 2006. The median age of the patients was 67 years (range = 29-93 years), with 56 percent older than age 65. Overall, 754 patients had received an immunomodulator, a proteasome inhibitor, or both as part of their initial therapy (59.9%, 22.6%, and 9.8%, respectively).
Dr. Majithia and colleagues then evaluated the survival difference between patients achieving at least a partial response to induction therapy and those who were primarily refractory to treatment.
The median overall survival from start of therapy was significantly shorter for the refractory group compared with patients who responded to therapy: 3.6 years versus 7.6 years, respectively (p<0.001). In addition, the difference in median overall survival persisted when only patients receiving a novel agent as part of induction therapy were considered (3.6 years vs. 7.9 years; p<0.001), and in a four-month landmark analysis (4.2 years vs. 7.6; p<0.001).
"We were also able to show that the depth of response to therapy correlated well with the outcomes in the era of novel therapies," Dr. Kumar said. The median overall survival for patients achieving some level of response from the four-month landmark in the patient groups (p<0.001 for all) were:
- Not reached for patients achieving a complete response
- 6.1 years for patients achieving a very good partial response
- 6.4 years for patients achieving a partial response
- 4.2 years for patients achieving less than a partial response
"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," the authors concluded. "When identified, [these factors] should be targeted for clinical trials." However, they did note that the nature of the study (its retrospective, non-randomized, and single-center design) limits the scope of these conclusions.
Majithia N, Rajkumar SV, Lacy MQ, et al. Outcomes of primary refractory multiple myeloma and the impact of novel therapies. Am J Hematol. 2015 July 27. [Epub ahead of print]