Treatment Strategies for Advanced Classic Hodgkin Lymphoma
The dacarbazine shortage has led to a crisis in managing patients with classic Hodgkin lymphoma (cHL). This crisis stems from the substantial loss of treatment efficacy that has resulted from attempts to omit dacarbazine from the combination chemotherapy regimen. Therefore, strategies for managing cHL during the dacarbazine shortage are crucial.
Strategies for optimally managing patients with advanced cHL as well as a treatment algorithm based on the patient’s fitness and ability to receive anthracyclines safely were provided in a review by Pallawi Torka, MBBS, MD, Roswell Park Comprehensive Cancer Center, Buffalo, NY, and colleagues (JCO Oncol Pract. 2022; doi:10.1200.OP.21.00890).
According to Dr Torka and the team, regimens based on the previous standard of care, namely mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), could serve as acceptable alternatives to the current standard of care, namely doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). However, mechlorethamine injection is no longer available in the Unites States. Therefore, for all practical purposes, MOPP has been replaced by cyclophosphamide, vincristine, procarbazine, and prednisone (COPP or C-MOPP).
Carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone (BCVPP) has compared favorably with MOPP in terms of complete response rate (CRR) and has showed less gastrointestinal and neurologic toxicity than MOPP. Other anthracycline-free alternative regimens include lomustine, vinblastine, and prednisone, which produced a better CRR than MOPP and was better tolerated but resulted in no difference in survival. Moreover, chlorambucil (Leukeran), vincristine, prednisone, and procarbazine (LOPP) produced a comparable CRR to MOPP but better overall survival (OS) and was better tolerated.
“Among all the available regimens, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) has the most robust evidence for substitution for ABVD,” wrote Dr Torka and colleagues, adding, “The BEACOPP regimen offers better disease control, although at the expense of greater short-term and long-term toxicities.”
In addition, bendamustine plus brentuximab is effective for relapsed or refractory HL, although data on its use as a first-line agent is limited. Another option may be brentuximab plus nivolumab, which produced a 52% complete response and an overall response rate of 61% in the ACCRU trial, although dose adjustments were required in 30% of patients to manage neurotoxicity.
To optimally manage the limited supply of dacarbazine, authors recommended forming a resource allocation team and establishing a process for approving alternative therapies. They also recommend having accurate data on the current supply and historical usage patterns to estimate how long dacarbazine supplies may last. Moreover, they wrote, “the current supply should be triaged to prioritize patients whose therapy cannot be changed and those without alternative acceptable options.” They also suggest dose rounding, vial sharing, and extending use of dacarbazine beyond its use date by compounding with closed systems transfer devices. “At minimum, patients can be scheduled on the same day to ensure that [dacarbazine] is used within its 72-hour shelf life,” they added.
In their suggested treatment algorithm, the review authors recommended escalated BEACOPP for young, fit patients, especially those with high-risk cHL. They suggested evaluating older patients with advanced cHL for anthracycline fitness and using COPP for patients unfit for anthracycline use. Moreover, they recommended single-agent brentuximab or brentuximab plus nivolumab for frail patients who are not candidates for chemotherapy.
