Health & Medical

Early Promise for Pembrolizumab Plus Chemo in RR Hodgkin’s Lymphoma

A chemoimmunotherapy regimen led to a 100% response fee as second-line remedy for relapsed/refractory (RR) classical Hodgkin lymphoma (cHL), a miniature segment II trial confirmed.

All 38 evaluable sufferers achieved aim responses with the combo of pembrolizumab (Keytruda), gemcitabine, vinorelbine, and liposomal doxorubicin (P-GVD), including entire responses in 36 of 38 cases. All nonetheless two of the sufferers attributable to this truth underwent high-dose remedy (HDT) and autologous hematopoietic cell transplantation (AHCT) and remained in remission after a median post-transplant apply-up exceeding a twelve months.

The outcomes counsel P-GVD has doable as an efficient and atmosphere friendly bridge to AHCT, nonetheless also elevate the quiz of whether every sufferers with RR cHL requires aggressive remedy, said Alison Moskowitz, MD, of Memorial Sloan Kettering Most cancers Heart in Contemporary York Metropolis, and colleagues, in the Journal of Clinical Oncology.

“The customary of care is for sufferers to catch a stem-cell transplant, so I feel the quiz now’s there any probability that there would possibly be a crew of sufferers who can care for far flung from that,” Moskowitz knowledgeable MedPage This day.

“We didn’t safe any distinction in response basically based fully on a patient’s stage or burden of illness,” she added. “The general response fee turned into once quite high, irrespective of whether sufferers had main refractory illness or relapsed illness, so I in actual fact think it’s miles an inexpensive formulation to grab into consideration for somebody who has relapsed/refractory illness. I feel the customary of care at this level would be to make use of a drugs savor this as a bridge to an autotransplant, and evaluation a nontransplant formulation is de facto investigational at this level.”

As many as 25% sufferers with developed-stage and 10% with early-stage cHL can maintain RR illness. Essentially the most modern customary of care is second-line remedy adopted by consolidation with HDT/AHCT, the authors illustrious.

Contemporary evaluation in RR illness maintain shown 2-twelve months development-free survival (PFS) of 70% or better. Key factors in improved outcomes maintain been pre-HDT/AHCT response by FDG-PET imaging and introduction of more moderen therapies, akin to brentuximab vedotin (Adcetris, BV), they continued.

No single customary-of-care second-line remedy exists for RR cHL, and several other quite loads of chemotherapy regimens maintain been shown to induce entire responses in 50%-60% of sufferers. Regimens that incorporate more moderen therapies, including BV and PD-1 inhibitors, maintain produced entire response charges of 67%-75%.

Data stay limited for results with incorporation of PD-1 blockade into second-line remedy, the authors continued. The combo of nivolumab (Opdivo) and BV can also furthermore be administered in the outpatient atmosphere with honest appropriate tolerability and results in end responses in two-thirds of sufferers and a 3-twelve months PFS of 77%.

Continuing the investigation of chemoimmunotherapy for R/R cHL, Moskowitz and colleagues evaluated P-GVD as second-line remedy earlier than HDT/AHCT. Investigators in the segment II, two-center trial enrolled 39 adult sufferers with R/R cHL, which turned into once main refractory illness in 41% of cases and relapse within 1 twelve months of frontline remedy in 38%.

Remedy consisted of two cycles of P-GVD in 31 sufferers and 4 cycles in the last eight. Response evaluation by FDG-PET came about after two cycles of remedy. Sufferers who achieved now not up to entire response got two more cycles of P-GVD, adopted by FDG-PET evaluation and consideration for HDT/AHCT. BV maintenance turned into once allowed following HDT/AHCT.

No dose-limiting toxicity came about, and most antagonistic events (AEs) had been grade 1/2 in severity. Essentially the most regularly reported AEs had been rash (49%), elevated liver enzymes (41%), oral mucositis (38%), nausea (36%), fatigue (31%), headache (23%), and infusion-connected reaction (21%). Grade 3 AEs consisted of four cases every of elevated liver enzymes and reduced neutrophil rely, two cases of oral mucositis, and one every of rash and hypothyroidism.

Immune-connected AEs included hyperthyroidism in 5 sufferers, transaminitis in 16, and rash in 19.

After two cycles of P-GVD, 35 of 38 (92%) sufferers achieved entire remission, and the last three sufferers had partial responses. Of seven sufferers who got an further two cycles of remedy, 5 achieved entire remission and two had partial responses.

Therefore, 36 of the 38 evaluable sufferers proceeded to HDT/AHCT. Thirteen sufferers got posttransplant BV and one got BV and nivolumab. Of the two sufferers who did now not undergo AHCT, one withdrew for private reasons after reaching a entire response to 2 cycles of P-GVD, and the quite loads of declined transplant in desire of off-perceive pembrolizumab maintenance. The patient who got pembrolizumab maintenance remained in remission 16 months after completing maintenance remedy.

Apply-up continues in the traditional cohort, and enrollment has begun in a second cohort of sufferers who can be handled with P-GVD, said Moskowitz. Additionally, correlative evaluation can be conducted in a perceive more insight to the remedy’s mechanism of motion and for doable biomarkers.

  • creator['full_name']

    Charles Bankhead is senior editor for oncology and likewise covers urology, dermatology, and ophthalmology. He joined MedPage This day in 2007. Apply


The perceive turned into once subsidized by Memorial Sloan Kettering Most cancers Heart and Merck Engaging & Dohme.

Moskowitz disclosed relationships with Seattle Genetics, Takeda, Imbrium Therapeutics, Merck, Janpix, Kyowa Kirin Global, miRagen, ADC Therapeutics, Bristol Myers Squibb, ADC Therapeutics, and BeiGene.

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