Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody

The biodistribution, toxicity, and therapeutic potential of anti-CD37 monoclonal antibody (MoAb) MB-1 labeled with iodine 131 (¹³¹I) was evaluated in ten patients with advanced-, low- or intermediate-grade non-Hodgkin's lymphomas who failed conventional treatment. Sequential dosimetric studies were performed with escalating amounts of antibody MB-1 (0.5, 2.5, 10 mg/kg) trace-labeled with 5 to 10 mCi ¹³¹I. Serial tumor biopsies and gamma camera imaging showed that the 10 mg/kg MoAb dose yielded the best MoAb biodistribution in the ten patients studied. Biodistribution studies in the five patients with splenomegaly and tumor burdens >1 kg indicated that not all tumor sites would receive more radiation than normal organs, and these patients were therefore not treated with high-dose radioimmunotherapy. The other five patients did not have splenomegaly and had tumor burdens <0.5 kg; all five patients in this group showed preferential localization and retention of MoAb at tumor sites. Four of these patients have been treated with ¹³¹I (232 to 608 mCi) conjugated to anti-CD37 MoAb MB-1, delivering 850 to 4,260 Gy to tumor sites. Each of these four patients attained a complete tumor remission (lasting 4, 6, 11+, and 8+ months). A fifth patient, whose tumor did not express the CD37 antigen, was treated with ¹³¹I-labeled anti-CD20 MoAb 1F5 and achieved a partial response. Myelosuppression occurred 3 to 5 weeks after treatment in all cases, but there were no other significant acute toxicities. Normal B cells were transiently depleted from the bloodstream, but immunoglobulin (Ig) levels were not affected, and no serious infections occurred. Two patients required reinfusion of previously stored autologous, purged bone marrow. Two patients developed asymptomatic hypothyroidism 1 year after therapy. The tolerable toxicity and encouraging efficacy warrant further dose escalation in this phase 1 trial.