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We’re Dropping G’s! … Golden Globule Awards for Lymphoma and Chronic Lymphocytic Leukemia

December 12, 2023
Nadine Abdallah, MD, (@nadineabdal), Joselle Cook, MBBS, (@JoselleCookMD
Division of Hematology, Mayo Clinic, Rochester, MN

This year, we decided to put an old-school 90’s hip-hop spin on the “Best of” series. We’re dropping G’s (AKA the “Golden Globule” awards) to some of the noteworthy oral abstracts in the lymphoma and chronic lymphocytic leukemia (CLL) world. Here goes! 

Hodgkin lymphoma (HL): The results of SWOG S1826 shook things up for HL earlier this year, heralding nivolumab (nivo)-doxorubicin, vinblastine, and dacarbazine (AVD) as a potential new standard-of-care therapy for advanced-stage disease. We got insight from the investigators on how older patients fared (Abstract 181 session 624). Here, Nivo-AVD prevailed over Brentuximab vedotin (BV)-AVD, demonstrating a one-year progression-free survival (PFS) rate of 93% vs. 64%, which was accompanied reductions in peripheral neuropathy and the number of high-grade infections.  

Mantle cell lymphoma (MCL) gets a Golden Globule for the SYMPATICO trial, which revealed impressive complete response (CR) and PFS rates (31.9 vs. 22.1 months) with venetoclax plus ibrutinib when compared with those for ibrutinib in relapsed/refractory (R/R) MCL (late-breaking abstract LBA2). Benefits were seen in all subgroups, including those with TP53-mutant disease. Another Globule went to Abstract 738, which focused on the phase II BOVen trial investigating the combination of zanubrutinib, obinutuzumab, and venetoclax in untreated TP53-mutant MCL. This combination resulted in a CR of 88%, with 71% of patients exhibiting minimal residual disease (MRD) negativity at the end of treatment. 

CLL: We dropped more Globule awards to the outstanding results of the BTK inhibitor (BTKi) and BCL-2i combinations, a key focus for CLL. In Abstract 631, Peter Hillmen, MBChB, PhD, provided long-term data from the phase III FLAIR study, affirming the efficacy of upfront venetoclax and ibrutinib and supporting the use of an MRD-based approach to guide treatment duration. Also in Abstract 633 presented long-term data from the phase II CAPTIVATE study, which showed excellent responses with ibrutinib re-treatment (overall response rate [ORR]: 86%) and a low rate of acquired resistance-associated mutations among progressors. On that note, looks like we may have a new power couple: sonrotoclax and zanubrutinib! Constantine S. Tam, MBBS, MD, showcased the safety and efficacy of this combination in patients with treatment-naïve CLL/small lymphocytic lymphoma (TN-CLL/SLL) (Abstract 327). Finally, updated results from the phase I BRUIN trial (Abstract 325) showcased the effectiveness of pirtobrutinib in heavily pretreated CLL despite prior BCL-2i/BTKi use.  

Richter transformation (RT): Trials aiming to improve outcomes for RT deserved some G’s. In Abstract 497, Adam S. Kittai, MD, described the dismal RT outcomes for patients with CLL who were pretreated with BCL-2i/BTKi. However, the chimeric antigen receptor (CAR)-T therapy associated survival data were encouraging. In Abstract 108, we saw an overall survival (OS) of 8.5 months  —  double that observed in historical cohorts! In Abstract 204, Othman Al-Sawaf, MD, discussed the standout ORR and survival results in a phase II trial of tislelizumab, a novel PD1 inhibitor, plus zanubrutinib for pretreated RT, in which neither duration of response nor OS was reached.  

Chimeric antigen receptor T-cell (CAR-T) therapies continue to transform outcomes for large B-cell lymphoma (LBCL). In Abstract 104, Jennifer L. Crombie, MD, presented the first real-world data for lisocabtagene maraleucel (liso-cel) in R/R LBCL, confirming favorable clinical trial results, even among patients with high-risk disease, with a CR rate of 65% and six-month PFS rate of 64%. In Abstract 103, we learned that bridging therapy prior to axicabtagene ciloleucel (axi-cel) did not affect responses but was associated with prolonged cytopenias. Clinical trial results don’t always translate into real-world outcomes, as shared in diffuse large B-cell lymphoma (Abstract 312). This session relayed the real-world results of loncastuximab in high-risk pretreated diffuse large B-cell lymphoma (DLBCL), which seemed less favorable than those reported in clinical trials, with an ORR of 33% (14% with CR) and 12-month PFS rate of only 12%. As patients with primary and secondary central nervous system lymphoma have typically been excluded from CAR-T trials, the real-world data from the EBMT registry Abstracts 192 and 1031 were particularly enlightening. Considering their historically dismal prognosis, it was heartening to see a two-year OS of 47% in this population. Circulating tumor DNA (ctDNA) has gained attention as a prognostic tool in DLBCL and was the focus of several abstracts. In Abstract 192, Mark Roschewski, MD, showed that ctDNA performed better than PET/CT for assessing residual disease and may be a useful complement to imaging to avoid additional testing and/or overtreatment. 

Last, but definitely not least, we’re dropping G’s to some of the abstracts that highlighted patient-reported outcomes (PROs). Abstract 669 focused on the impact of ongoing bispecific therapy with odronextamab on function and quality of life (QoL) among patients with R/R follicular lymphoma in the phase II ELM-2 trial. This represents a thoughtful inclusion of PROs in an early-phase trial, looking beyond global QoL to symptoms and function over time. The rare and painful cutaneous T-cell lymphomas got some much-deserved attention in Abstract 381 in which changes between health-related QoL (HRQoL) were correlated with skin-related QoL and treatment response. Finally, Amber Koehler, PA-C, reported data for the largest longitudinal series of adult CLL survivors (Abstract 498). This study disclosed similar QoL scores between patients in the “watch-and-wait” and treatment groups in the novel therapy era, but lower scores with treatment in the chemoimmunotherapy era. These data support the role of interventions to improve QoL in patients with CLL, with additional analyses forthcoming. 

While these were our Golden Globule picks, the high quality of all the oral (and poster) sessions was a powerful testament to the ongoing commitment to improving the lives of patients with CLL and lymphoma globally. What were some of your other top picks? Tell us at @nadineabdal @JoselleCookMD!  

Drs. Abdallah and Cook indicated no relevant conflicts of interest. 

 

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