A Study of Safety and Efficacy of Nivolumab and Bendamustine (NB) in Patients With Relapsed/Refractory Hodgkin Lymphoma After Nivolumab Monotherapy Failure

Lepik, Kirill V.; Mikhailova, N.B.; Kondakova, Elena; Zalyalov, Y.; Fedorova, L.; Tsvetkova, L.; Kotselyabina, P.V.; Borzenkova, E.; Babenko, Elena V.; Popova, M.; Darskaya, Elena I.; Baykov, Vadim; Moiseev, Ivan S.

doi:10.1097/hs9.0000000000000401

Cited by 16 publications

(11 citation statements)

References 22 publications

(64 reference statements)

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“…In addition, only three patients treated with the combined approach were consolidated successfully with allo-SCT. In a prospective phase II trial, Lepik and colleagues 8 treated 30 patients with nivolumab plus bendamustine after nivolumab monotherapy failure, obtaining an overall response and CR rates of 87% and 57%, respectively. Interestingly, nine patients (30%) had been previously refractory to bendamustine.…”

Section: Discussionmentioning

confidence: 99%

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Addition of chemotherapy to nivolumab after PD-1 inhibitor failure as bridge to allogeneic stem cell transplantation in classical Hodgkin’s lymphoma: report on three cases and literature review

Romero

Balaguer‐Roselló

Montoro

et al. 2021

Therapeutic Advances in Hematology

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The poor prognosis of refractory or relapsed (R/R) classical Hodgkin’s lymphoma (cHL) after autologous stem cell transplantation has improved greatly due to the introduction of brentuximab vedotin and PD-1 inhibitors. However, the duration of response achieved with these novel agents is too short. The information about the management of patients after anti-PD-1 therapy failure is very limited in cHL, although chemotherapy alone or combined with PD-1 inhibitors has shown encouraging results. We report three cases of heavily pretreated cHL, refractory to nivolumab monotherapy, successfully rescued with the addition of chemotherapy to nivolumab, as a bridge to allogeneic stem cell transplantation (allo-SCT). All three patients presented poor clinical features such as three to four previous lines including brentuximab vedotin and autologous stem cell transplantation, refractoriness to the last line of therapy previous to nivolumab, and rapid disease progression. Notwithstanding these characteristics and nivolumab failure, they achieved a complete response after the addition of chemotherapy, were consolidated with allo-SCT, and still remain in complete response. There are few studies concerning the combination of PD-1 inhibitors and chemotherapy after nivolumab failure, including one retrospective study and one phase II trial with nivolumab plus bendamustine. Therefore, only few patients are consolidated with allo-SCT. However, there are several ongoing trials investigating new combinations of chemotherapy and PD-1 inhibitors in R/R cHL, as well as in first line. All these data suggest that anti-PD-1 therapy may reprogram the immune system, activating and inhibiting effector and immunosuppressive cells, respectively, leading to overtake of chemorefractoriness. Allo-SCT can increase the immune-related events of patients treated with anti-PD-1 previously, consistent on acute graft- versus-host disease, sinusoidal obstruction syndrome, and noninfectious febrile syndrome. In conclusion, the combination of PD-1 inhibitor and chemotherapy may be a feasible therapy after anti-PD-1 treatment failure as a bridge to allo-SCT.

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Section: Discussionmentioning

confidence: 99%

“…CT alone or in combination with PD-1 inhibitors has shown encouraging responses in some patients. 7 , 8 Radiotherapy has also been useful due to the potential synergism with PD-1 inhibitors and the abscopal effect. 9 …”

Section: Introductionmentioning

confidence: 99%

Addition of chemotherapy to nivolumab after PD-1 inhibitor failure as bridge to allogeneic stem cell transplantation in classical Hodgkin’s lymphoma: report on three cases and literature review

Romero

Balaguer‐Roselló

Montoro

et al. 2021

Therapeutic Advances in Hematology

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“…Combination therapies involving BV (a CD30-direct-Tarekegn et al World J Oncol. 2021;12(4):81-84 ed antibody-drug conjugate) and nivolumab and ipilimumab; nivolumab and bendamustine; nivolumab with radiation therapy are being developed [17][18][19][20].…”

Section: Combination Therapymentioning

confidence: 99%

“…Given this, combination therapy has been pursued. Combination therapies involving BV (a CD30-directed antibody-drug conjugate) and nivolumab and ipilimumab; nivolumab and bendamustine; nivolumab with radiation therapy are being developed [ 17 - 20 ].…”

Section: Combination Therapymentioning

confidence: 99%

Checkpoint Inhibitors in Relapsed/Refractory Classical Hodgkin Lymphoma

et al. 2021

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Even though classical Hodgkin lymphoma is highly curable, the outcome of patients with a refractory or relapsed disease has been disappointing. Multiple lines of therapy are available for patients after their first failure, and most respond to subsequent therapies. However, there is a sizable proportion that remains relapsing/recurrent even after several lines of therapy. The overall prognosis of patients with relapsing and recurrent classical Hodgkin lymphoma (rrcHL) has been very disappointing until recently. Immune checkpoint inhibitors such as the anti-programmed death 1 (PD-1) receptor antibodies have recently been approved to treat relapsed and refractory cHL and have significantly improved the outcome of patients with rrcHL. The approved immune checkpoint inhibitors for relapsed and refractory cHL are nivolumab and pembrolizumab. In the Checkmate 205 study nivolumab demonstrated an objective response rate of 69% with an acceptable safety profile. Similarly, pembrolizumab demonstrated an overall response rate (ORR) of 69% with a complete remission rate (CRR) of 22.4% in the KEYNOTE-087 study in heavily pretreated patients with rrcHL.

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“…The combination of avelumab and agents hypothesized to augment antitumor immunity, including chemotherapy, may be a beneficial therapeutic strategy for patients with R/R DLBCL. Current clinical data support concurrent treatment with an immune checkpoint inhibitor and chemotherapy in solid tumors [26] and classic Hodgkin lymphoma [27].…”

Section: Introductionmentioning

confidence: 98%

Avelumab in Combination Regimens for Relapsed/Refractory DLBCL: Results from the Phase Ib JAVELIN DLBCL Study

et al. 2021

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Background Relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis despite the availability of multiple treatment options. Preliminary evidence suggests that DLBCL may be responsive to programmed death ligand 1 (PD-L1)/programmed death 1 inhibitors. Objective The JAVELIN DLBCL study was conducted to assess whether a combination of agents could augment and sustain the antitumor immunity of avelumab, an anti-PD-L1 antibody, in R/R DLBCL. Methods This was a multicenter, randomized, open-label, parallel-arm study with a phase Ib and a phase III component. Reported here are the results from the phase Ib study, wherein 29 adult patients with DLBCL were randomized 1:1:1 to receive avelumab in combination with utomilumab (an immunoglobulin G2 4-1BB agonist) and rituximab (arm A), avelumab in combination with utomilumab and azacitidine (arm B), or avelumab in combination with bendamustine and rituximab (arm C). The primary endpoints were dose-limiting toxicities and objective response as assessed by the investigator per Lugano Response Classification criteria. Results Of the seven patients in arm A, one (14.3%) experienced two grade 3 dose-limiting toxicities (herpes zoster and ophthalmic herpes zoster); no dose-limiting toxicities were reported in arms B or C. No new safety concerns emerged for avelumab. One partial response was reported in arm A, three complete responses in arm C, and no responses in arm B. Given the insufficient antitumor activity in arms A and B and the infeasibility of expanding arm C, the study was discontinued before initiation of the phase III component. Conclusions The low level of clinical activity suggests that PD-L1 inhibitor activity may be limited in R/R DLBCL. ClinicalTrials.gov Identifier NCT02951156. Key PointsAvelumab, an anti-programmed death ligand 1 (PD-L1) antibody, was assessed in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in combination with therapies hypothesized to augment antitumor immunity.The low level of clinical activity for avelumab combinations suggests that PD-L1 inhibitor activity may be limited in R/R DLBCL.

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A Study of Safety and Efficacy of Nivolumab and Bendamustine (NB) in Patients With Relapsed/Refractory Hodgkin Lymphoma After Nivolumab Monotherapy Failure

Cited by 16 publications

References 22 publications

Addition of chemotherapy to nivolumab after PD-1 inhibitor failure as bridge to allogeneic stem cell transplantation in classical Hodgkin’s lymphoma: report on three cases and literature review

Addition of chemotherapy to nivolumab after PD-1 inhibitor failure as bridge to allogeneic stem cell transplantation in classical Hodgkin’s lymphoma: report on three cases and literature review

Checkpoint Inhibitors in Relapsed/Refractory Classical Hodgkin Lymphoma

Avelumab in Combination Regimens for Relapsed/Refractory DLBCL: Results from the Phase Ib JAVELIN DLBCL Study

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