Should We Treat Biochemical Relapse in Multiple Myeloma?

When determining treatment for a patient with relapsed multiple myeloma (MM), one of the first questions to consider is whether the patient’s relapse is symptomatic or asymptomatic. Clearly, a patient with a symptomatic clinical relapse should be treated with consideration for the duration of their response to previous therapy in addition to other factors such as age, performance status, comorbidities, and previous/residual treatment-related toxicities. However, some patients experience biochemical relapse, in which M protein increases in the absence of organ dysfunction or CRAB symptoms (hypercalcemia, renal impairment, anemia, or bone lesions). Most patients with biochemical relapse will progress to clinical relapse, with a median time of approximately 5 months. However, a small fraction of patients—approximately 20%—may remain in biochemical relapse without progression for several years. For this reason, some clinicians prefer to delay treatment until the patient has a clinical relapse.

In the randomized phase III ENDEAVOR study of carfilzomib/dexamethasone vs bortezomib/dexamethasone in relapsed/refractory MM, the investigators conducted a post hoc subgroup analysis of PFS and OS outcomes of patients treated in biochemical relapse vs those in clinical relapse. These results show a clear benefit of early intervention. Median PFS and OS were both prolonged with treatment at the time of biochemical relapse compared with clinical relapse. That was true for both treatment arms, but the best outcomes were seen in patients who received carfilzomib/dexamethasone at biochemical relapse. Neither median PFS or OS was reached in this group of patients vs a median PFS of 17.7 months and a median OS of 44.0 months with the same treatment given upon clinical relapse. This is a typical paradigm for MM; earlier intervention is generally best for the patient, in my opinion. By contrast, waiting may allow the malignant clone to expand, making the MM cells more resistant to subsequent therapy. With a few exceptions, such as older patients with nonaggressive disease at presentation, I prefer to treat patients with MM at the time of biochemical relapse.

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