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

O. W. Press, J. F. Eary, C. C. Badger, P. J. Martin, F. R. Appelbaum, R. Levy, R. Miller, S. Brown, W. B. Nelp, Kenneth Krohn, D. Fisher, K. DeSantes, B. Porter, P. Kidd, E. D. Thomas, I. D. Bernstein

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Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)1027-1038
Number of pages12
JournalJournal of Clinical Oncology
Volume7
Issue number8
StatePublished - 1989
Externally publishedYes

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Non-Hodgkin's Lymphoma
Anti-Idiotypic Antibodies
Monoclonal Antibodies
Therapeutics
Splenomegaly
Neoplasms
Tumor Burden
Radioimmunotherapy
Hypothyroidism
Radionuclide Imaging
Iodine
Immunoglobulins
B-Lymphocytes
Bone Marrow
Radiation
Biopsy
Antigens
Antibodies
Infection

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Press, O. W., Eary, J. F., Badger, C. C., Martin, P. J., Appelbaum, F. R., Levy, R., ... Bernstein, I. D. (1989). Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody. Journal of Clinical Oncology, 7(8), 1027-1038.

Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody. / Press, O. W.; Eary, J. F.; Badger, C. C.; Martin, P. J.; Appelbaum, F. R.; Levy, R.; Miller, R.; Brown, S.; Nelp, W. B.; Krohn, Kenneth; Fisher, D.; DeSantes, K.; Porter, B.; Kidd, P.; Thomas, E. D.; Bernstein, I. D.

In: Journal of Clinical Oncology, Vol. 7, No. 8, 1989, p. 1027-1038.

Research output: Contribution to journalArticle

Press, OW, Eary, JF, Badger, CC, Martin, PJ, Appelbaum, FR, Levy, R, Miller, R, Brown, S, Nelp, WB, Krohn, K, Fisher, D, DeSantes, K, Porter, B, Kidd, P, Thomas, ED & Bernstein, ID 1989, 'Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody', Journal of Clinical Oncology, vol. 7, no. 8, pp. 1027-1038.
Press OW, Eary JF, Badger CC, Martin PJ, Appelbaum FR, Levy R et al. Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody. Journal of Clinical Oncology. 1989;7(8):1027-1038.
Press, O. W. ; Eary, J. F. ; Badger, C. C. ; Martin, P. J. ; Appelbaum, F. R. ; Levy, R. ; Miller, R. ; Brown, S. ; Nelp, W. B. ; Krohn, Kenneth ; Fisher, D. ; DeSantes, K. ; Porter, B. ; Kidd, P. ; Thomas, E. D. ; Bernstein, I. D. / Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody. In: Journal of Clinical Oncology. 1989 ; Vol. 7, No. 8. pp. 1027-1038.
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abstract = "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 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.",
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AU - Press, O. W.

AU - Eary, J. F.

AU - Badger, C. C.

AU - Martin, P. J.

AU - Appelbaum, F. R.

AU - Levy, R.

AU - Miller, R.

AU - Brown, S.

AU - Nelp, W. B.

AU - Krohn, Kenneth

AU - Fisher, D.

AU - DeSantes, K.

AU - Porter, B.

AU - Kidd, P.

AU - Thomas, E. D.

AU - Bernstein, I. D.

PY - 1989

Y1 - 1989

N2 - 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 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.

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