Professor Steven Le Gouill from the Centre Hospitalier Universitaire de Nantes, France, takes  delegates through state-of-the-art management of relapsed/refractory mantle cell lymphoma (R/R MCL) at the Janssen H3 medical education symposium in Melbourne.

“MCL is one of those conditions where management has traditionally been more of an art than a science. While we have guidelines, they can be difficult to follow because each patient is very different.¹ The past dicates the future, where the treatment we choose next depends on what the patient has had before, their duration of response and comorbidities,” he began.

How soon should we consider chemotherapy alternatives?

Prof. Le Gouill commented that while there’s a plethora of chemotherapy options available,² “we don’t have head-to-head comparisons. If you have a patient who has failed on one regimen, you need to consider what their response was and what other chemotherapy regimens remain. However, we now have the Bruton’s tyrosine kinase (BTK) inhibitors which offer us chemotherapy-free alternatives.^3,4 The question that remains is, given so many chemotherapy options are available, should we switch away at the first relapse? Again, it’s going to be a decision based on the patient sitting infront of you. But BTK inhibitors like ibrutinib can be given at the first relapse.^5,6

Where should BTK inhibitors sit when it comes to the R/R MCL patient?

“As an alternative to chemotherapy regimens, which involve multiple agents, ibrutinib is a single oral drug option.⁵ The phase 2 trial PCYC-1104 demonstrated that in 111 patients with a median of three prior therapies, the overall response rate (ORR) was 68%, with 21% achieving a complete response (CR).⁷ The phase 3 RAY trial was comparing the non-chemotherapy standard of care (SOC) at the time – temsirolimus.⁸ At the 2-year landmark, the PFS rate was 41% for ibrutinib vs 7% for temsirolimus.⁸ The OS rates were not drastically different given confounding due to crossover from temsirolimus to ibrutinib, but overall ibrutinib reduced the risk of death in the relapsed patient by 24%,”⁸ explained Prof. Le Gouill.

“In 2017, results of a pooled analysis of all the ibrutinib trials, PCYC-1104, SPARK and RAY trials confirmed that response rates to ibrutinib are better when used earlier.⁹ More patients achieved a CR with only one prior line (37.4%) vs 23.3% in patients with more than one prior line of therapy.”⁹ 

Prof. Le Gouill presented data showing how this translated across progression-free survival (PFS) and overall survival (OS) as well.⁹

“Generally, Grade 3/4 adverse events (AEs) were less common in patients with only one prior line of therapy,”⁹ he continued.

“While ibrutinib can be used from the first relapse,^5,6 we still don’t have clinical trial evidence comparing ibrutinib versus chemoimmunotherapy at first relapse or whether it matters if a patient has relapsed early or late. For now we have to make our own call in each case,” he cautioned.  

The future is looking full of more options

Prof. Le Gouill then took the delegates through some of the trials of other BTK inhibitors not yet available “Looking at the BTK inhibitors coming through, we need to keep in mind that we were already aware of the side effect profile of BTK inhibitors, so trials have been designed with this in mind,” he noted.

When it comes to the ongoing role of allograft in MCL, Prof. Le Gouill admitted his stance on this point has been controversial at times. “On this topic, I’ve had a crowded room against me citing the many other options available today. But I do it without any doubt in young patients as it remains our best chance at cure we have,” he said.

In concluding, Prof. Le Gouill reminded delegates that at present, at first relapse “we have the choice between rituximab-based chemotherapy, BTK inhibitor-based chemotherapy or even allo-stem cell transplant for fit, chemotherapy-refractory/early relapse patients. As for the pipeline of trials, there’s a lot we have to learn but what we won’t get any time soon is an answer of chemotherapy vs BTK inhibitors. That’s going to be something left for us to decide in practice.”

This article was sponsored by Janssen, which has no control over editorial content. The content is entirely independent and based on published studies and experts’ opinions, the views expressed are not necessarily those of Janssen.

References:

1. Dreyling M, et al. Ann Oncol 2017;28(suppl 4):iv62-iv71.
2. Ladha A, et al. Exp Hematol Oncol 2019;8:2.
3. McKay P, et al. Br J Haematol. 2018 Jul;182(1):46-62.
4. Campo E, et al. Blood. 2015 Jan 1;125(1):48-55.
5. IMBRUVICA (ibrutinib) Approved Product Information, 19 July 2018.
6. Australian Government. Department of Health. Pharmaceutical Benefits Scheme. Available at: www.pbs.gov.au (accessed 3 June 2019).
7. Wang ML, et al. N Engl J Med 2013;369(6):507-516.
8. Rule S, et al. Blood 2015;126:469.
9. Rule S et al. Haematologica 2019;104:e214.