ABVD-Based Regimens May Improve Survival in CLL that Transforms to Hodgkin Lymphoma

Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-based therapy regimens may help to prolong the survival of patients with chronic lymphocytic leukemia (CLL) who develop Hodgkin lymphoma (HT), according to results of a multicenter retrospective study published in Haematologica.

Richter transformation (RT) occurs in 5% to 10% of all CLL patients and clinical outcomes are exceedingly poor. The median overall survival is only 5 to 8 months from diagnosis. Typically, in the majority of RT cases, the CLL transforms in diffuse large B-cell lymphoma. The development of Hodgkin lymphoma in CLL patients occurs in just 1%. The survival for this patient population ranges from 0.8 to 3.9 years after diagnosis.

Ninety-four patients with HT CLL were identified across 13 centers for the analysis. The median age at the time of HT diagnosis was 67 (range, 38-85) and 81% were male. Eighty-seven percent of patients had an Ann Arbor stage of 3/4 and 68% had an ECOG performance status of 0 or 1. Eleven percent had bulky disease and 65% had B-symptoms. In terms of pathology subtype, 59^ had type 1 HT and 57% were Epstein Barr virus. The median number of CLL-directed therapies prior to HT diagnosis is 2 (range, 0-12). Therapies observed included no therapy (18%), no cytotoxic chemotherapy (29%), purine analogue-based therapy (46%), Ibrutinib (Imbruvica)-based therapy (27%), acalabrutinib (Calquence)-based therapy (2%), venetoclax (Venclexta)-based therapy (1%), both cytotoxic chemotherapy and ibrutinib-based therapy (16%), and both purine analogue and ibrutinib-based therapy (13%).

At a median follow-up of 1.6 years (range, 0.0-15.1), the median time between HT diagnosis and HT treatment was 15 days. The median progression-free survival (PFS) was 21 months (95% CI, 14-58). The estimated 2-year survival was 48% (95% CI, 38%-61%). Additionally, patients who received any CLL-directed therapy prior to HT had a lower 2-year overall survival (OS) than those who did not. In patients who received prior CLL-directed therapy, the 2-year OS was 69% (95% CI, 58%-82%) compared with 95% in patients who didn’t receive any prior CLL-directed therapy (95% CI, 82-100. P =.02). 

However, in patients who developed HT following ibrutinib treatment, the estimated 2-year OS was slightly higher than those who did not receive ibrutinib prior to HT (73% vs 64%). However, this was found to not be statistically different (P =.33). The median time from treatment with any ibrutinib to HT was 15.5 months (range, 1.2-37.7). 

Compared with patients who received ABVD-based therapy (n = 48) as first therapy for HT, those who received rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (n = 8), had a similar risk of death (HR, 1.6, 95% CI, 0.4-5.7 P =.48).

Additionally, patients who received doxorubicin hydrochloride (Adriamycin), bleomycin sulfate, vinblastine sulfate, and dacarbazine (AVD)-based therapy (n = 9) or other (n = 9) regimens as first-line therapies for HT had an increased risk of death compared to those who received an ABVD-based regimen. This analysis remained significant after adjusting for age.

In patients who received hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) (n = 7), 2-year OS was 67% (95% CI, 38%-100%). This was similar to the 72% 2-year OS observed in the 87 patients who did not undergo HSCT in CR1 (95% CI, 63-74).

“In our study, the majority of patients [61%] only received one line of HL therapy and only 20% went on to receive HSCT [7% while in CR1]. Although limited by small numbers, the patients who underwent HCT for HT in CR1 had a similar 2-year OS to patients who did not undergo HCT for HT in CR1. Our data indicate that these patients with HT can have prolonged OS after achieving response to first-line therapy for HT and may not require HCT in CR1. Therefore, our large series does not support the recommendation of HCT in CR1 for this patient population and has major implications in the management of these patients,” wrote study authors.

_REFERENCE:

_{Stephens DM, Boucher K, Kander E, et al. Hodgkin lymphoma arising in patients with chronic lymphocytic leukemia: outcomes from a large multi-center collaboration. Haematologica 2020;106(11):2845-2852; doi: 10.3324/haematol.2020.256388.}