Plasma cell myeloma. An interpretive review

Abstract

Melphalan (M), cyclophosphamide (Cy), and BCNU are effective in the treatment of myeloma, producing objective improvement in a direct manifestation of the disease in 35 to 50% of patients, and prolonging survival to approximately 20 months from the start of therapy. Procarbazine is also effective, but the toxicity of prednisone for myeloma cells is questioned. Since the average myeloma tumor‐doubling time is about 6 months, the improved survival of myeloma patients associated with M treatment can be explained on the basis of a tumor cell kill of approximately one log. Mouse and human plasma cell tumors resistant to M have been shown to be sensitive to Cy, and concurrent M + BCNU, and M + Cy are synergistic against the KHT fibrosarcoma. The following approaches may improve treatment: 1. evaluate two, or more, alkylating agents administered sequentially, or concurrently; 2. test cycle‐specific agents after treatment with alkylating agents, and 3. use mouse myelomas resistant to M, Cy, and BCNU to screen new agents.

Cyclophosphamide’s addition in relapsed/refractory multiple myeloma patients with biochemical progression during lenalidomide‐dexamethasone treatment

“…We chose cyclophosphamide (CTX), an alkylating agent without cross‐resistance to melphalan, with a well‐established activity in MM . A series of clinical trials performed in the UK in the 1980s demonstrated the equivalent efficiency of cyclophosphamide compared to melphalan with a favorable toxicity profile, with less profound myelosuppression, making it safe to use in patients eligible for transplantation .…”