Ipilimumab plus Lenalidomide after Allogeneic and Autologous Stem Cell Transplantation for Patients with Lymphoid Malignancies.

Abstract

Purpose: Prevention or treatment of relapsed lymphoid malignancies after hematopoietic stem cell transplantation (HSCT) requires novel strategies. We hypothesized that antitumor-cell responses could be enhanced by the addition of lenalidomide to the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab.Experimental Design: We conducted a phase II investigator-initiated trial to assess the safety and activity of ipilimumab and lenalidomide in patients with lymphoid malignancies that relapsed after allogeneic HSCT and in high-risk patients after autologous HSCT. Patients received 10 mg of oral lenalidomide daily for 21 days followed by intravenous ipilimumab at 3 mg/kg bodyweight. The regimen was repeated 4 weeks later for a total of four treatments.Results: We enrolled 17 patients (10 allogeneic and seven autologous transplant recipients). Immune-mediated toxicity was limited to one patient with asymptomatic hypothyroidism and one with dermatitis in the allogeneic and autologous groups, respectively. One allogeneic transplant recipient had a flare of prior GVHD while taking lenalidomide that precluded further treatment. All others finished treatment without GVHD. Four of 10 patients in the allogeneic group had complete responses (three of which were durable at 19+, 21+, and 32+ months), and three had partial responses. The disease in six of seven patients in the autologous group remains in remission. The groups had similar immune responses, including a two- to threefold increase in inducible ICOS+CD4+FoxP3- T-cell number.Conclusions: Our early-phase data suggested that ipilimumab plus lenalidomide is well tolerated after HSCT. Adverse events did not differ significantly between the allogeneic and autologous groups. Clin Cancer Res; 24(5); 1011-8. ©2017 AACR.

• Authors: Issa F Khouri, Irina Fernandez Curbelo, Francesco Turturro, Elias J Jabbour, Denái R Milton, Roland L Bassett Jr, Luis M Vence, James P Allison, Alison M Gulbis, Padmanee Sharma
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 24 Issue 5 Pg. 1011-1018 (03 01 2018) ISSN: 1557-3265 [Electronic] United States
• PMID: 29246938 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Ipilimumab
• Lenalidomide

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• CD4-Positive T-Lymphocytes (drug effects, immunology)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Graft vs Host Disease (chemically induced, epidemiology, immunology)
• Hematopoietic Stem Cell Transplantation (adverse effects, methods)
• Humans
• Ipilimumab (administration & dosage, adverse effects)
• Lenalidomide (administration & dosage, adverse effects)
• Lymphoma (immunology, pathology, therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (immunology, pathology, therapy)
• Pilot Projects
• Transplantation, Autologous (adverse effects, methods)
• Transplantation, Homologous (adverse effects, methods)
• Treatment Outcome