At the 65th ASH Annual Meeting in San Diego, California, Yucai Wang, MD, PhD, Mayo Clinic, Rochester, Minnesota, examines findings from the SHINE trial, which indicated that first-line bendamustine-rituximab and second-line Bruton’s tyrosine kinase (BTK) inhibitor therapy yielded highly efficacious outcomes among patients with mantle cell lymphoma (MCL). 

Transcript:

Hi, my name is Yucai Wang. I'm from Mayo Clinic in Rochester, Minnesota. I'm a lymphoma clinical investigator there. I'm here at the ASH 2023 [meeting] in San Diego. In this study, we examined the outcome[s] of mantle cell lymphoma following frontline bendamustine-rituximab (BR), and second-line [Bruton's tyrosine kinase] (BTK) inhibitor therapy.

For patients with mantle cell lymphoma [who] are older or unfit, the current standard of care for frontline therapy is bendamustine-rituximab chemotherapy, followed by optional rituximab maintenance therapy. The preferred second-line therapy is a BTK inhibitor. Whether moving BTK inhibitor all the way to the frontline to combine with bendamustine-rituximab chemotherapy can improve patient outcomes remains unclear at this point. 

Several trials are addressing this question. SHINE started out last year [and] they reported that the addition of ibrutinib to bendamustine-rituximab, rituximab maintenance, improved progression-free survival, but not overall survival. In this setting, people wonder whether the cumulative progression-free survival with the first-line BR and the second-line BTK inhibitor used in a sequential manner can match that of the [progression-free survival] (PFS) of the combination of bendamustine-rituximab and BTK inhibitor. 

We tried to address this question by modeling observational data in the retrospective setting. So, 26 centers in the United States participated in this study. We had a total of 651 patients with mantle cell lymphoma that started BR in the frontline between 2014 to 2020. We specifically examined the outcomes after the first-line BR and the second-line BTK inhibitor, and more importantly, the so-called [event-free survival] (EFS)-2 using the intention to treat framework, measuring the event-free survival from first-line BR start all the way to second line event. 

The patient population appears very similar to that reported in the SHINE population, with the exception that maybe we have more TP53-mutated patients in the tested population and also slightly more patients with the blastoid and polymorphic variant. In terms of outcomes, first-line BR resulted in an event-free survival of approximately 3 years. If we're looking at the EFS-2 from first line slide to the second line BTK, the median EFS-2 was 68 months. 

Considering in our study, only 40% of the patients received maintenance. We think this cumulative EFS-2 from first-line and second-line BTK in [the] intention to treat analysis appears very reasonable. [In reference to] SHINE, [the trial] started reporting a median PFS of 80 months for their combination therapy. Again, considering the differences in routine practice versus trial population, the use of rituximab maintenance of 40 versus 80% in the trial and when to use a BTK inhibitor, we think the outcomes following the sequential treatment strategy appear very reasonable and appear [to match] that of the combination therapy.

The main takeaway from this study is, with SHINE not practice-changing, and with this retrospective data, we think using BR in the frontline and a reserve[ing] BTK for the second line in a sequential manner is a very reasonable treatment approach for patients with mantle cell lymphoma. 

Source: 

Wang Y, Larson MC, Hwang SR, et al. Multicenter study of mantle cell lymphoma outcomes following first-line bendamustine-rituximab and second-line Bruton’s tyrosine kinase inhibitor therapy. Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 300