Monday, December 6, 2021

ASH Preview: R-Squared (Lenalidomide + Rituximab)

As I said a few weeks ago, I was surprised at how many ASH presentations this ear are focusing on Lenalidomide (also known as Revlimid), either in combination with Rituxan (to make R-Squared) or combined with other treatments. I probably shouldn't be surprised. When R-Squared was shown to be as effective as Rituxan + chemo, it opened up a lot of possibilities. The idea of effective treatments that don't involve traditional chemotherapy (like CHOP or Bendamustine) is very attractive to patients and to doctors.

I may review a few more of those presentations at some point, but the two that have caught my attention most are these:  

2417 Six-Year Results from the Phase 3 Randomized Study Relevance Show Similar Outcomes for Previously Untreated Follicular Lymphoma Patients Receiving Lenalidomide Plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed By Rituximab Maintenance 

3532 Ten Year Follow up of the MD Anderson Cancer Center Phase 2 Study of Rituximab in Combination with Lenalidomide (R2) for Patients with Low Tumor Burden Follicular Lymphoma 

The studies are a little different from one another, but similar in that they are fairly long-term studies of R-Squared, and both show very good long-term results for Follicular Lymphoma patients.

The 6 year study (number 2417) is part of the RELEVANCE trial, which looks at R-Squared in previously untreated FL patients (that is, the R-Squared would be their first treatment). Patients are either given R-Squared and then Rituxan Maintenance, or are give immunochemotherapy followed by maintenance. Importantly, all of the 1030 patients had high tumor burden -- lots of FL in their bodies. The results in the abstract might be a little confusing, because they do the analysis two different ways (one by the researchers themselves, and the other a little more objectively). Either way, the results are good, and after 6 year follow-up, the R-Squared patients are very close to the Chemo patients, in terms of effectiveness and safety. The Progression-Free Survival after 6 years was 60% for R2 and 59% for chemo, and the Overall Survival was 89% for both groups, and there were no new side effects issues reported. The data confirms that R-Squared is a good alternative to traditional chemo for high tumor burden FL patients who have not received treatment. that's pretty great news.

The 10 year study (number 3532 above) looks at a different population -- FL patients with LOW tumor burden, though they also had not received any other treatment. This is also a much smaller study -- only 40 patients. But the results are similar. The Overall Response Rate was 98%, with 39 patients getting a Complete response and 1 getting a Partial Response. (One patient dropped out of the study before finishing, which is why the ORR is 98% and not 100%). After 10 year follow-up, the Progression-Free Survival rate (the lymphoma came back) was 59%, the Time to Treatment Failure (starting a second treatment) was 82%, and the Overall Survival was 95%. This study did not have two arms  -- that is, unlike the 6 year study, it didn't have half of patients taking R2 and half taking chemo. They all took R2 for this one. But the numbers are pretty similar to the 6 year study, and even add a few years on to the median follow-up.

Taken together, the lesson seems to be that we can expect more doctors to consider R-Squared as a first-line treatment for Follicular Lymphoma. There will still be lots of options (R-CHOP, R-B, straight Rituxan, watch-and-wait, plus lots of clinical trials), but my guess is that more oncologists will consider the option. Chemo is generally more effective than Rituxan or W and W, but with more side effects. R2 gives similar effectiveness, but with different (maybe less harsh) side effects than chemo.

It would be nice to have easy answers for which treatments will be most effective for individual patients (see my last post), but for now, I guess we can be glad that there are options available for us.

More to come soon.









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