Highly active chemotherapy-free diet in R / R Hodgkin lymphoma

Three-quarters of patients with relapsed / refractory Hodgkin lymphoma remained alive without disease progression 3 years after treatment with nivolumab (Opdivo) and brentuximab vedotin (Adcetris), a prospective multicenter trial showed.

Patients who underwent autologous stem cell transplantation (ASCT) after treatment with nivolumab-brentuximab had a 3-year progression-free survival (PFS) of 91%. The 3-year overall survival (OS) was 93%.

Adverse events were generally mild or moderate and self-limiting. Adverse events related to the immune system requiring systemic corticosteroids occurred in 18% of patients, reported Ranjana H. Advani, MD, of Stanford University in Calif., And colleagues, in Some blood.

“BV (brentuximab vedotin) and nivolumab as initial lifesaving therapy, along with ASCT, were well tolerated and provided long-lasting remissions in a high proportion of patients with relapsed / refractory classical Hodgkin lymphoma (r / r cHL) “, the authors concluded. “These data continue to support the promise of combining BV and nivolumab as a highly active and well-tolerated rescue regimen and potentially offering an alternative to chemotherapy-based rescue in patients with r / r cHL.”

The authors of an accompanying editorial agreed that “this regimen has the potential to provide an alternative to cytotoxic chemotherapy regimens such as ifosfamide, carboplatin, and etoposide as the first lifesaving treatment, if the results are confirmed in a randomized trial “.

“The optimal sequencing of the brentuximab-nivolumab regimen with standard salvage chemotherapy and other immunotherapies and the evolutionary role of stem cell transplantation (SCT) in relation to highly active second-line rescue regimens remain important questions for practitioners. future studies, ”said Yun Choi, MD, and Catherine Diefenbach, MD, both of Perlmutter Cancer Center at NYU Langone Health in New York City.

“Future studies of relapsed HL should focus on questions of what are the most effective salvage transplant regimens and whether there are therapies that can avoid the need for TSS in certain subsets of patients.” , they added. “Advani et al provide a compelling rationale to further study the brentuximab-nivolumab regimen in a randomized fashion with other regimens to answer the first question, but the last question will be more difficult to address.”

10% to 30% of patients with cLH are refractory to the initial treatment or relapse after the initial response. Salvage chemotherapy followed by ASCT remains the standard of care, and patients who achieve a complete metabolic response after salvage chemotherapy have significantly better long-term relapse-free survival after ASCT. As a result, the identification of treatment regimens that are both well tolerated and offer high complete response rates has been the subject of ongoing research, the authors noted in their introduction.

Brentuximab vedotin antibody-drug conjugate has been shown to have monotherapy activity in r / r cHL. BV has also shown promise as a lifesaving therapy when given sequentially or in combination with chemotherapy, the authors continued. Nivolumab has also shown promise as a treatment for r / r LHc, resulting in an objective response rate of 73% and complete responses of 28%. BV and nivolumab are generally well tolerated, which justifies the evaluation of the combination in r / r cHL.

Researchers conducted a multicenter, single-arm phase I / II trial involving adults with biopsy-proven r / r HLc. The protocol excluded patients who had previously received lifesaving treatment. Staggered and same-day dosing of BV and nivolumab were evaluated during the trial. At the end of BV-nivolumab treatment, patients could proceed to TSA at the discretion of the investigator. Adverse events related to the immune system occurred in 16 patients, none of whom discontinued treatment.

Data analysis included 91 patients who received treatment. The combination of BV and nivolumab resulted in an objective response rate of 85%, including a complete response rate of 67%. Subsequently, 67 patients underwent ASCT. After a median follow-up of 34.3 months, the estimated PFS was 77% in all patients and 91% in those who underwent ASCT.

The most common treatment-related adverse reactions prior to ASCT were nausea (52% of patients), infusion-related reactions (43%), and fatigue (40%), all except one grade I / II (one fatigue episode level 3). A total of 30 grade ≥3 adverse events occurred, including five cases of neutropenia. Two patients discontinued due to adverse events (one each with peripheral neuropathy and gamma-glutamyltransferase).

  • Charles Bankhead is editor-in-chief for oncology and also covers urology, dermatology and ophthalmology. He joined MedPage Today in 2007. To follow

Disclosures

The study was supported by Seagen and Bristol Myers Squibb (BMS).

Advani disclosed relationships with Agensys, Celgene, Forty Seven, Genentech, Infinity Pharma, Janssen, Kura, Merck, Millennium Pharma, Pharmacyclics, Regeneron, Seagen, AstraZeneca, Autolus, Mayer, Celmed, Gilead and Takeda.

Diefenbach disclosed relationships with BMS, Seattle Genetics, Genentech, and Merck.


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