Katja Weisel, MD
In Part 1 of this editorial, Katja Weisel, MD, of University Hospital Tubingen in Germany, describes the benefits of longer treatment in patients with multiple myeloma.
Despite recent progress in advancing the care of patients with multiple myeloma (MM), this cancer remains incurable.
Although novel combination regimens have driven major improvements in patient outcomes, most MM patients still experience multiple relapses, even those who respond to treatment initially.1
Historically, MM was treated for a fixed duration, followed by a treatment-free interval and additional treatment at relapse. However, evidence suggests that continuous therapy after an initial response may be a better approach.2,3
Pooled data from three large, phase 3 trials in newly diagnosed MM patients suggest that continuous therapy may lead to an increase in progression-free survival (PFS) and overall survival (OS).2
These results are supported by a meta-analysis, which showed favorable outcomes in PFS and OS with lenalidomide maintenance compared to placebo or observation in newly diagnosed MM patients who had received high-dose therapy and autologous stem cell transplant.3
Given these emerging findings and the availability of effective and tolerable therapies suitable for longer use, there is an opportunity to increase the adoption of this treatment strategy to improve outcomes for MM patients.
The concept of longer treatment for MM is not new. The first clinical trials in which researchers evaluated the efficacy and safety of this approach were conducted 40 years ago in patients initially treated with melphalan and prednisone. However, modest efficacy and substantial toxicity limited longer treatment with those agents.4-7
The intervening years saw the introduction of new agents with different mechanisms of action, such as proteasome inhibitors and immunomodulators. These therapies, commonly used as initial treatment, provided physicians with additional options for treating patients longer.
Research has shown that longer treatment with immunomodulatory agents and proteasome inhibitors can be clinically effective.8
Longer treatment—integrated in the first-line treatment strategy and before a patient relapses—may enhance conventional induction strategies, resulting in better PFS and OS.9,10
Continuous treatment, in which a patient receives treatment beyond a fixed induction period, has demonstrated extended PFS and OS as well.2,3
Data supporting the benefits of prolonged therapy with immunomodulatory drugs has been a key driver behind the shifting paradigm in favor of longer treatment as the standard of care.11,3
Additionally, continuing treatment with a proteasome inhibitor beyond induction therapy is associated with an improvement in the depth of response and prolonged OS.12
Longer treatment with proteasome inhibitors is also associated with deepening response rates and improved PFS following hematopoietic stem cell transplant.13-15
Recent research has also shown that patients may achieve deeper remission with longer treatment,16,17 overturning the long-held belief that longer duration of therapy can only extend a response rather than improve it.
Moreover, treating patients for longer may now be possible because of the favorable toxicity profile of some of the novel therapies currently available, which have fewer cumulative or late-onset toxicities.18
Dr. Weisel has received honoraria and/or consultancy fees from Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda. She has received research funding from Amgen, Celgene, Sanofi, and Janssen.
The W2O Group provided writing support for this editorial, which was funded by Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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