Myelomatosis: Comparison of Melphalan and Cyclophosphamide Therapy

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.

Plasma cell myeloma. An interpretive review

Bergsagel

1972

Plasma cell leukemia: Detailed studies and response to therapy

Shaw¹,

Twele²,

Nordquist³

1974

A case of plasma cell leukemia (PCL) was shown by immunoelectrophoretic and immunofluorescent studies to be producing kappa light chains. Cyto‐chemical staining of the cells revealed strong β‐glucuronidase, oil red 0, and acid phosphatase positivity. Electron microscopy demonstrated various stages in plasma cell development. A good partial remission was obtained following a combination regimen of cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Intermittent high dosage melphalan and prednisone were used at a later stage. PCL may have an improved prognosis using aggressive combination chemotherapy.

Cross-resistance to alkylating agents in multiple myeloma

Bladé

Feliú

Rozmán

et al. 1983

In order to ascertain whether multiple myeloma patients resistant to one alkylating agent would respond to a second one, high‐dose intermittent cyclophosphamide was administered to 12 patients showing resistance to melphalan and prednisone. On the other hand, intermittent melphalan and prednisone treatment was employed in eight myeloma patients resistant to intermittent cyclophosphamide. Only one objective response was achieved among 12 patients on cyclophosphamide therapy, in spite of having employed high doses of this alkylating agent. No responses were achieved with melphalan in the group of cyclophosphamide‐resistant patients. The median survival probability was 8.7 months (SD ± 2.9) for all patients after starting the second alkylating agent. These results suggest cross‐resistance between melphalan and cyclophosphamide in myeloma. The authors conclude that a single second alkylating agent cannot be recommended as a treatment of patients with multiple myeloma who are truly refractory to one alkylating agent.