Defining a new treatment strategy for curing cHL chemotherapies

07 Jul 2021

As classical Hodgkin lymphoma (cHL) has a high cure rate, Prof. Kwong, Yok-Lam emphasized that all cHL patients should be considered curable when deciding the optimal treatment strategy, with the therapeutic goal being achieving remission in every cHL case. In practice, clinicians should utilize positron emission testing/computed tomography (PET/CT) for diagnosis and follow-up after treatment. “The primary aim is to achieve remission in every patient and clinicians should consider every patient with cHL to be potentially curable. Of course, we cannot cure everybody, but the starting point must be that these patients are curable,” underlined Prof. Kwong.

Currently, doxorubicin, bleomycin, vinblastine plus dacarbazine (ABVD) remains as the standard first-line regimen for cHL treatment.1 However, for patients with stage III/IV cHL, brentuximab vedotin with doxorubicin, vinblastine and dacarbazine (A+AVD) has demonstrated an improved 3-year progression-free survival (PFS) of 83.1% versus 76.0% in ABVD (HR=0.704; 95% CI: 0.550-0.901; p=0.005), and is adopted by Prof. Kwong’s team for treating patients with advanced stage and unfavorable disease.1 For elderly patients who cannot tolerate routine chemotherapy, nivolumab plus brentuximab vedotin (BV) has demonstrated a median PFS of 18.3 months with 52% of patients achieving complete response (CR).2

Despite available treatment, about 15-20% of cHL patients will have disease relapse and develop relapsed/refractory cHL (rrcHL).3 Although salvage chemotherapy followed by autologous-hematopoietic stem-cell transplantation (AHSCT) are still considered the standardof- care for transplant eligible rrcHL patients in many countries, Prof. Kwong noted that the practice these days has shifted away from AHSCT in young patients as transplantation may sterilize them. In Queen Mary Hospital, a non-HSCT strategy is adopted and AHSCT DEFINING A NEW TREATMENT STRATEGY FOR CURING cHL WITHOUT CHEMOTHERAPIES is now only performed when the patient no longer responds to anti-programmed cell death protein 1 (PD-1) therapy.

Although only 25% of patients can achieve durable response, BV remains an effective salvage therapy for rrcHL with a median PFS of 9.3 months.4 In patients failing chemotherapy and BV, pembrolizumab treatment resulted in a 24-month PFS of 44.2%.5 For patients who failed autologous-HSCT, pembrolizumab also achieved a significantly longer median PFS (13.2 vs. 8.3 months; 95% CI: 0.48-0.88; p=0.00271), objective response rate (ORR; 65.6% vs. 54.2%) and duration of response (DOR; 20.7 vs. 13.8 months) than BV.6 Given its effectiveness, anti-PD-1 may be considered ahead of BV in practice, with their combination offered to patients who can afford both medications. “If a patient presents with rrcHL, you ought to start with anti-PD-1 instead of BV as the initial salvage. If the patient can afford it, it may be advantageous to combine the two treatments,” noted Prof. Kwong.

To address the concerns of toxicity associated with anti-PD-1 therapy, Prof. Kwong and his team adopt a low-dose approach when treating rrcHL patients. Where standard dose nivolumab (240mg Q2W) and pembrolizumab (200mg Q3W) had achieved an ORR of 69% and 72%, and a CR of 16% and 28%, respectively, the low-dose approach in local practice (nivolumab 40mg Q2W and pembrolizumab 100mg Q3W) had improved the ORR of both treatments to 100% and CR to 73% and 67%, respectively.7 With this impressive result, Prof. Kwong noted that PD-1 blockade should be incorporated into the treatment of rrcHL. In fact, cHL may be one of the lymphoid malignancies to be cured entirely by a non-chemotherapy approach. “I honestly believe that in the next several years, we will be able to define treatment strategies for patients with cHL where no chemotherapies will be given,” concluded Prof. Kwong.

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