Radioimmunotherapy with 177Lu-DOTA-rituximab: final results of a phase I/II Study in 31 patients with relapsing follicular, mantle cell, and other indolent B-cell lymphomas

J Nucl Med. 2013 Jul;54(7):1045-52. doi: 10.2967/jnumed.112.115170. Epub 2013 Apr 9.

Abstract

The aim of this study was to determine the maximum tolerated dose (MTD) and to explore the clinical response to (177)Lu-DOTA-rituximab in the treatment of patients with relapsed follicular, mantle cell, or other indolent lymphomas such as marginal zone lymphoma.

Methods: To evaluate the MTD, we adjusted the dosage of the radiopharmaceutical according to body surface area (BSA).

Results: The MTD using (177)Lu-DOTA-rituximab was 1,665 MBq/m(2) of BSA. Thrombocytopenia and leukopenia were the dose-limiting toxicities. Significant anemia occurred only at dose level 7 (1,850 MBq/m(2) of BSA). We observed the nadir of platelets after a median of 36 d from treatment and the nadir of granulocytes after a median of 50 d. Median time to recovery to the next lower grade of toxicity was 7 d. Nonhematologic toxicity was negligible. We observed clinical responses at all dose levels and for all lymphoma entities. Some of the responses were durable; the longest follow-up is currently over 8 y. At present, 11 patients are alive and 8 patients are disease-free.

Conclusion: Our results demonstrate the safety and feasibility of (177)Lu-DOTA-rituximab treatment for the lymphoma entities tested in this study.

Keywords: 177Lu; lymphoma; radioimmunotherapy; rituximab.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Dose-Response Relationship, Radiation
  • Female
  • Humans
  • Lymphoma, B-Cell / diagnostic imaging
  • Lymphoma, B-Cell / radiotherapy*
  • Lymphoma, Follicular / diagnostic imaging
  • Lymphoma, Follicular / radiotherapy*
  • Lymphoma, Mantle-Cell / diagnostic imaging
  • Lymphoma, Mantle-Cell / radiotherapy*
  • Male
  • Middle Aged
  • Organometallic Compounds / administration & dosage*
  • Organometallic Compounds / adverse effects
  • Radiation Injuries / diagnosis
  • Radiation Injuries / etiology
  • Radioimmunotherapy / methods*
  • Radionuclide Imaging
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / adverse effects
  • Recurrence
  • Rituximab
  • Treatment Outcome

Substances

  • 177Lu-DOTA-rituximab
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Rituximab