Long-Term Updates on Chemotherapy-Free Lenalidomide Plus Rituximab Treatment for MCL

Jia Ruan, MD, PhD, Weill Cornell Medicine, New York, New York, shares 9-year follow-up findings from a phase 2 trial on the outcomes of chemotherapy-free lenalidomide plus rituximab combination therapy among patients with mantle cell lymphoma (MCL), which demonstrated highly effective and durable responses in this patient population. 

Transcript:

Hi, this is Dr. Jia Ruan. I'm a lymphoma physician at Weill Cornell. I specialize in treating patients with all kinds of lymphoma, and I do a lot of research in a subtype of lymphoma called mantle cell lymphoma. 

Today, I want to share with you our study results for an investigator-initiated phase 2 study that looked at the efficacy, [or] effectiveness, and safety of a combination with lenalidomide-rituximab. It is a combination that [is] free of conventional chemotherapy. It was developed over 10 years ago when we just entered the novel agent era for a patient with mantle cell lymphoma. 

Prior to that, most of the patients were treated with chemoimmunotherapy, some of which could be quite intensive with a lot of side effects. We also know that to this day there's no cure with initial therapy. So, our rationale at that point was looking for a treatment combination that [is] effective and also well tolerated, and that can preserve the quality of life for patients with mantle cell lymphoma.

Coming onto the study design for the phase 2 lenalidomide plus rituximab [study], the study included 2 phases. The first is the induction phase, during which the patients received oral lenalidomide 3 weeks on and 1 week off. In addition, they also received rituximab infusion, which is once a week for 4 doses for month 1, and subsequently every other month. After 12 cycles of induction treatment, patients would enter maintenance where lenalidomide continues for 3 weeks on 1 week off at a lower dose, and rituximab maintenance also continues every other month. Patients could [stay] on the treatment for 3 years, and some of them go beyond. 

We were very pleased with the effectiveness of this combination. The overall response rate was over 90% and over 60% [of] patient[s] achieved complete remission. Importantly, the durability of the response was quite impressive. We have about ⅔ of the patients who remain lymphoma-free. Their progression-free survival was over 68% at 5 years. 

Recently, we just tallied our outcome with a median of 9 years of follow-up. [The] 9-year progression-free survival was over 50%. That translates to half of the patients continuing to be free of lymphoma and have not seen additional therapy. In fact, following the treatment with lenalidomide-rituximab, they have not seen chemotherapy and many of them continue to lead a very productive lifestyle with very minimal side effects. 

Certainly, we are very, very careful in terms of monitoring side effects. The initial side effects included asymptomatic cytopenia, so we do see neutropenia without fever.

During the induction phase, we adjust our lenalidomide dosing to maintain adequate neutrophil counts. We're also monitoring patients for the occurrence of secondary malignancy, which remains to be a risk factor for anybody who has lymphoma and getting treatment. Overall, we're very, very encouraged and I think the results [are] quite powerful.

It is the very first study that uses a chemotherapy-free combination. As we know now, there are so many more options with novel agents, the most important class is [Bruton’s tyrosine kinase] (BTK) inhibitor, which has shown to be the most effective single agent for patients with mantle cell lymphoma. We have seen the combination of BTK inhibitors with rituximab and other agents. I think, overall, these chemo-free options really present a very effective treatment for our patients with mantle cell lymphoma.

Looking ahead, I think that the important questions are how do we prioritize patients' treatment based on their risk factors for the disease? How does the novel combination compare with chemoimmunotherapy? There are phase 3 trials ongoing comparing BTK plus rituximab combination with chemoimmunotherapy. We look forward to the outcome of those important studies. Thank you.

Source: 

Yamshon S, Chen G, Gribbin C, et al. Nine-year follow-up of lenalidomide plus rituximab as initial treatment for mantle cell lymphoma. Published online: September 8, 2023. Blood Adv. doi:10.1182/bloodadvances.2023010606