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Quadruplet Versus Triplet Therapy for Multiple Myeloma

By: Lauren Harrison, MS
Posted: Wednesday, January 23, 2019

A carfilzomib-containing quadruplet combination seems to be well tolerated and associated with “deep responses” both before and after autologous stem cell transplant in patients with newly diagnosed multiple myeloma. Graham H. Jackson, MD, of the Northern Institute for Cancer Research, Newcastle upon Tyne, UK, and his colleagues presented their data from the randomized phase III Myeloma XI trial comparing quadruplet and triplet therapies at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 302) in San Diego and published them in the journal Blood.

“The benefit of upfront intensification of treatment persisted even compared to triplets administered sequentially and including exposure to both lenalidomide and bortezomib,” reported the investigators.

A total of 1,056 patients were randomly assigned to receive a minimum of 4 cycles of either KCRD in 28-day cycles, CRD in 28-day cycles, or CTD in 21-day cycles. KCRD included carfilzomib, cyclophosphamide, lenalidomide, and dexamethasone; CRD included cyclophosphamide, lenalidomide, and dexamethasone; CTR included cyclophosphamide, thalidomide, and dexamethasone.

After a median of 34.5 months, those treated with the quadruplet regimen was found to have a significantly longer progression-free survival than those treated with triplet therapy for all cytogenetic-risk groups (hazard ratio = 0.63). The time to second objective disease progression (PFS2) was also significantly improved in the quadruplet group; the 3-year PFS2 was 81.8% with KCRD compared with 75.1% with triplet therapy. Those treated with KCRD also had deeper responses than those treated with triplet therapy before and after transplant, according to the investigators.

Generally, the KCRD regimen did not produce significant additional toxicity compared with the other two treatments. Grade 3 or higher neutropenia occurred in 16.4% of patients treated with KCRD, 22.3% of those treated with CRD, and 12.8% of those treated with CTD. However, thrombocytopenia occurred in 8.4% of the KCRD group, 2.3% of the CRD group, and 1.2% of the CTD group.

Disclosure: The study authors’ disclosure information can be found at bloodjournal.org.



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