Fixed duration vs continuous therapy in multiple myeloma

Abstract

The introduction of new drugs with less severe toxicity profiles than those of conventional antimyeloma agents allowed the evaluation of continuous therapy compared with fixed duration therapy. In transplant-eligible patients, consolidation therapy with bortezomib or bortezomib-based regimens showed significant progression-free survival (PFS) benefit in cytogenetic standard-risk patients and to a lesser extent, high-risk patients. Continuous therapy with lenalidomide maintenance treatment after autologous stem cell transplantation resulted in a significant survival gain. In transplant noneligible patients, continuous lenalidomide-dexamethasone therapy improved survival over fixed duration melphalan-prednisone-thalidomide. The concept of prolonged treatment in elderly patients is supported by some other studies, but most of them revealed a gain in PFS only. Young patients with unfavorable prognosis show a greater willingness to accept long-term treatment, whereas the readiness to undergo such treatments and the benefits therefrom decline with increasing age and decreasing fitness, rendering fixed duration therapy a suitable option in elderly frail patients.

Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma

“…Among the potential benefits are suppression of clonal evolution (recognizing that emergence of drugresistant clones is also a potential risk that could limit future treatment options) 18 ; however, this hypothesis needs demonstrating in randomized controlled trials and is currently based on expert assumptions. Similarly, other potential benefits include sustained control of disease symptoms, immune modulation, and continued cytoreduction leading to unmeasurable residual diseaseoptimally, complete eradication of MM cells 2 . Deepening of response is an important goal, as deeper responses 19 (and sustained deep response 20 ) are associated with improved outcomes.…”

“…Ongoing increases in progression-free (PFS) and overall survival (OS) are being seen with novel regimens across treatment settings, associated with the evolving paradigm of long-term treatment approaches, including continuous therapy and maintenance, which can prolong disease control and improve PFS and sometimes OS compared to fixed-duration approaches 2,3 . Definitions of therapeutic approaches within this paradigm of long-term treatment are summarized in Table 1 4,5 . This paradigm is being increasingly followed, with safety profiles of newer drugs improving long-term treatment feasibility vs. older agents 2 . Various long-term approaches in newly diagnosed MM (NDMM) are discussed within current guidelines and recommendations 1,[6][7][8][9][10] .…”

Different Patient Subgroup Different Maintenance, Proteasome Inhibitors or Immunomodulators Maintenance for Newly Diagnosed Multiple Myeloma: A 7-Year Single-Center Data in China

“…Moreover, the patients did not receive maintenance therapy partly because of their poor physical condition. Our limited sample size may also have had an impact on the results, but the survival benefit of maintenance therapy is beyond reasonable doubt (8)(9)(10)(11)(12)(13)(14). Various maintenance treatment options for NDMM are recommended within consensus guidelines (15)(16)(17).…”

Lenalidomide Maintenance After Autologous Stem Cell Transplant: The Utility of Real-World Data and Future Areas of Study

“…The upcoming Dana Farber partner analysis of the IFM2009 study (NCT01191060) in which maintenance lenalidomide was continued until progression has yet to read out, which potentially implies a superior PFS with this non-finite approach. Therefore, a definitive answer to the question of whether lenalidomide maintenance should always be continued until disease progression remains unanswered for now, particularly in the era of MRD testing, but our current policy continues to advocate continuous administration until myeloma relapse [6,43].…”