Optimizing outcomes in relapsed/refractory Hodgkin lymphoma: a review of current and forthcoming therapeutic strategies

Abstract

The outcome of patients with relapsed/refractory classical Hodgkin lymphoma (rr-cHL) has improved considerably in recent years owing to the approval of highly active novel agents such as brentuximab vedotin and Programmed Death-1 (PD-1) inhibitors. Although no randomized trials have been conducted to provide formal proof, it is almost undisputable that the survival of these patients has been prolonged. As autologous stem-cell transplantation (SCT) remains the standard of care for second-line therapy of most patients with rr-cHL, optimization of second-line regimens with the use of brentuximab vedotin, or, in the future, checkpoint inhibitors, is promising to increase both the eligibility rate for transplant and the final outcome. The need for subsequent therapy, and especially allogeneic SCT, can be reduced with brentuximab vedotin consolidation for 1 year, while pembrolizumab is also being tested in this setting. Several other drug categories appear to be active in rr-cHL, but their development has been delayed by the appearance of brentuximab vedotin, nivolumab and pembrolizumab, which have dominated the field of rr-cHL treatment in the last 5 years. Combinations of active drugs in chemo-free approaches may further increase efficacy and hopefully reduce toxicity in rr-cHL, but are still under development.

Current Use of Total Body Irradiation in Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation

“…Autologous HSCT is usually preferred over allogeneic HSCT as a salvage option for both Hodgkin and non-Hodgkin lymphomas. 27 28 Allogeneic HSCT has been performed less frequently than salvage chemotherapy or autologous HSCT because it is generally associated with high treatment-related mortality (TRM) despite the relatively strong possibility of being completely cured. 28 29 30 31 32 …”

Konsensus ekspertów Polskiej Grupy Badawczej Chłoniaków w zakresie postępowania w nawrotowym lub opornym na leczenie klasycznym chłoniaku Hodgkina w 2020 roku

“…Prawdopodobieństwo nawrotu choroby w przypadku negatywnego wyniku PET/CT po chemioterapii ratunkowej nie przekracza 40%. Natomiast w przypadku nieuzyskania CMR przed auto-HCT prawdopodobieństwo to jest znacznie wyższe, sięga bowiem 60-75% [19].…”

“…Nie ma bezpośrednich badań, w których porównano by poszczególne schematy, co powoduje brak przyjętego standardu postępowania. W konsekwencji wybór leczenia drugiej linii opiera się na doświadczeniu i preferencjach ośrodka leczącego, stanie klinicznym pacjenta, obecności chorób współistniejących, rodzaju stosowanego leczenia pierwszej linii (kumulacyjna dawka antracyklin i bleomycyny) [12,15,[19][20][21]. Ostatnio obiecujące wyniki uzyskano za pomocą schematu opartego na bendamustynie i gemcytabinie (BeGeV) z odsetkiem CR sięgającym 73% [22] oraz za pomocą schematu BGD (bendamustyna, gemcytabina, deksametazon) [23].…”

Combination of PD‐1 inhibitor with GVD (gemcitabine, vinorelbine, liposomal doxorubicin) versus GVD regimen as second‐line therapy for relapsed/refractory classical Hodgkin lymphoma

“…1,2 Although nearly 70% of all patients with cHL can be cured by the standard first-line chemotherapy with or without localised radiotherapy, treatment failure still occurs in ˜30% of the cases. 2,3 Conventional salvage chemotherapy followed by autologous stem cell transplantation (ASCT) with or without radiotherapy is the standard treatment for patients who are relapsed or refractory to the first-line treatment. 4,5 However, only about half of the patients with relapsed/refractory (r/r) cHL can be salvaged by the second-line treatment and achieve long-term remission.…”