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

Abstract

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. 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. 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 ICOSCD4FoxP3 T-cell number. 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. .

Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation

“…Another cohort of 15 patients received ipilimumab at the dose of 5 mg/kg (2, 13). Ipilimumab was given to 10 patients at 3 mg/kg for a total of 2 doses, alternating with lenalidomide (9). In another study, 3 patients received ipilimumab for five cycles with no information available on the dose (12).…”

“…Investigators reported 35 deaths of which, 10 cases (28%) were GVHD related. Nine studies reported prior history of GVHD in 49% patients (1, 7–9, 13, 16, 20, 26, 27). Complications, other than GVHD, include hematologic side effects (22%), most notably neutropenia; followed by respiratory and hepatic complications (16% and 14% respectively).…”

Updated Results of Rituximab Pre- and Post-BEAM with or without 90Yttrium Ibritumomab Tiuxetan during Autologous Transplant for Diffuse Large B-cell Lymphoma

“…Instead, IPI > 0 immediately preceding stem cell collection and the number of chemotherapy regimens received prior to transplantation were predictive of OS, DFS and relapse. Innovative strategies such as the use of immunotherapy post-transplantation in this setting are currently undertaken at our center (30).…”

<p>Role of Stem-Cell Transplantation in Leukemia Treatment</p>

“… 88 Although it serves as an alternative treatment method, HSCT still has a relapse risk among 40%–80% of recipients. 89 Both auto-HSCT and allo-HSCTare the main alternative cellular therapeutic methods to treat leukemia. Auto-HSCT is the appropriate and applicable therapeutic option for multiple myeloma 1 , 18 and HL.…”