Treatment of plasma cell myeloma with cytotoxic agents.

Because cross-resistance between alkylating agents has not been observed, we attempt in a prospective trial to determine the advantages, if any, in administering three alkylating agents sequentially, alternately, or concurrently. A patient with myeloma, showing progressive shortening of M-protein doubling time from 98 to 15 days, developed an acute terminal phase, characterized by fever and pancytopenia. A similar acute terminal phase was observed in 17 of 50 deaths from myeloma. Since alkylating agents are only effective in controlling the chronic phase of myeloma, future improvements will require the discovery of agents that delay, prevent, or are effective in the treatment of the acute phase. Forty-five patients with kappa- and 36 with lambda-light-chain disease showed no differences in frequency of amyloidosis, renal failure, response to treatment, or survival after treatment with alkylating agents.