Low-Dose Radiation Effective With/Without Concurrent Chemotherapy in R/R Mantle Cell Lymphoma

Matthew S. Ning, MD, MPH

Matthew S. Ning, MD, MPH

Low-dose radiotherapy of 4 Gy is both safe and effective as a treatment for relapsed/refractory patients with mantle cell lymphoma (MCL) across different sites of active disease, according to an analysis conducted at The University of Texas MD Anderson Cancer Center.

Overall, 19 patients with 98 sites of relapsed/refractory MCL were treated with low-dose radiotherapy between 2014 and 2018. The median follow-up was 51.3 months from initial diagnosis and 15.4 months after receiving the radiation treatment. Additionally, 15 patients had classical histology and the remaining 4 patients had blastoid variant. Seventy-four sites were refractory to ongoing chemotherapy at the time of receiving low-dose radiotherapy.

Fourteen of the 19 patients received concurrent chemotherapy; 4 patients started concurrent therapy 3 to 6 months prior to radiation and 10 had started concurrent therapy within 1 month of initiating radiation. For the 5 patients that were treated without concurrent chemotherapy, their last systemic therapy preceded the initial radiation by a median of 24 months.

A complete remission (CR) was achieved in 79 of the 98 total sites (81%), with a median time to CR of 2.7 months. Overall, 11% of the CRs were achieved within 1 month, 44% by 2 months, and 36% after 3 months. Additionally, 5 sites achieved a partial response. The overall response rate was 86%. The 1-year overall survival rate was 90%, and the 1-year progression-free survival (PFS) rate was 55%.

Investigators did not observe any radiotherapy-related toxicities. Overall, low-dose radiotherapy with concurrent chemotherapy was well-tolerated, according to this analysis.

Although this study was small, it demonstrated that low-dose radiotherapy can be given to a subset of patients with MCL with no additional toxicities. The treatment can be given with concurrent chemotherapy safely and lead to promising responses. A phase II trial is already underway at MD Anderson Cancer Center to further investigate this treatment option (NCT04054167).

In an interview withTargeted Oncology, Matthew S. Ning, MD, MPH, of the Department of Radiation Oncology, UT MD Anderson Cancer Center, discussed the role for low-dose radiotherapy as treatment of patients with relapsed/refractory MCL, according to the findings from a recent analysis. He also highlighted how a multidisciplinary approach can impact the treatment of patients with MCL.

TARGETED ONCOLOGY: What was the rationale for conducting this study?

Ning:We have been treating patients with MCL here at MD Anderson and these patients, in particular, although they only represent 6% of the non-Hodgkin lymphoma population, represent a very challenging cohort. MCL is a rare subtype, but it can be very aggressive and generally demonstrates a multiply recurrent cohort with poor outcomes. Although these patients respond to first-line therapy, they relapse frequently and develop chemotherapy-refractory disease.

Further action requires multidisciplinary collaboration here; we’ve kind of done this with our medical oncologist colleagues here, we’ve had an excellent multidisciplinary relationship, as is the culture here at MD Anderson. Together, we came up with this novel concept to utilize radiation therapy in part of the definitive management of these patients— not just palliating sites, like some of these other centers do, but by addressing all sites of active disease. It’s interesting that MCL is exquisitely radiosensitive. We’re talking about very low doses of radiation here, 4 Gy, which is a relatively low-dose radiation and is associated with very minimal side effects. However, it’s often overlooked in the treatment of these complex patients.

When these patients run out of chemotherapy options, radiation therapy can address the sites with high effectiveness. This used to be reserved as a particular unique indication with just a few patients treated in the early 2000s, but now many of these patients are being referred to our clinic for consolidation with radiation therapy.

TARGETED ONCOLOGY: What were the methods of design for this study?

Ning:The study design came about after Bouthaina S. Dabaja, MD, realized that she had treated and potentially granted cures for many of these patients in the clinic. They were coming back for follow-up, and their lesions had completely disappeared with this low dose of radiation. They also didn’t have any toxicity, so we decided to systematically analyze this and look at all the patients we have treated as such at our institution to see, quantitatively, how they’ve done.

TARGETED ONCOLOGY: What were the findings from this analysis?

Ning:I pooled all the patients from our department, and I analyzed their charts, their entire history of follow-up as well as their initial presentation. Altogether, we were very pleased with the findings. We demonstrated excellent local control, very high in almost 85% of these sites. We demonstrated excellent 1-year PFS rates for these patients with respect to all active sites of disease. The best part is they didn’t have to stop concurrent chemotherapy and they had no toxicities. We are talking about treatments in some very sensitive areas, including the bowel and spinal cord, where the traditional doses of radiation therapy result in toxicities for a lot of these patients. Here, however, it’s a very high therapeutic ratio because it’s all benefit in terms of disease control without any of the adverse effects.

TARGETED ONCOLOGY: What patients will benefit most from this low-dose radiotherapy?

Ning:I think certainly more patients are being referred across the country, and even internationally, for low-dose radiation therapy. There are significantly more patients that could benefit from this treatment approach. That’s why we tried to rush to get these data published; it’s a relatively small amount of patients right now, but we have solid follow-up. With our findings, we wanted to convey this to a national audience to get [physicians] to start thinking about this and talking about this with their extra-disciplinary collaborators and consider this as a feasible treatment option for these patients who have limited options at this point.

TARGETED ONCOLOGY: Are there any next steps planned for investigating the role of low-dose radiotherapy in these patients?

Ning:Right now, Dr Dabaja and Dr Michael Wang are collaborating on a similar prospective phase II study, particularly for ibrutinib [Imbruvica]-refractory patients who demonstrate some of the most aggressive courses of disease. With this prospective study, we can definitively quantify the real benefits with this approach.

TARGETED ONCOLOGY: Can you speak to how it can be incorporated more into clinical practice?

Ning:In the evolving field of oncology as a whole, there is an increase in collaboration, discussion, and multidisciplinary conversation overall with all members of the team, including medical oncology and radiation oncology, as well as others like surgical oncology (which plays an important role for other non-hematologic sites). We hope that this analysis demonstrates the importance of attending multidisciplinary conferences, advocating for patients, and coming up with multi-tier strategic multidisciplinary treatment plans in the patient’s best interest.

TARGETED ONCOLOGY: What should a community oncologist take away from this research?

Ning:In the community setting, there is sometimes a concern for different resource allocation, compared with what’s available at academic cancer centers, such as MD Anderson, but what we want to emphasize in this case is that the radiation therapy that benefited these patients was treated to multiple sites in many cases and resulted in low toxicity, even though these patients were getting concurrent chemotherapy, which is often a concern in terms of toxicity for higher radiation courses. Even though we typically advocate for referral of these patients to academic cancer centers, from a community standpoint, if there is appropriate multidisciplinary collaboration and care, this is a very feasible and safe treatment modality in the sense that there were no toxicities associated with this. All benefits were appreciated without even grade 2 toxicities associated with this radiation therapy.

Reference:

Ning MS, Pinnix CC, Chapman BV, et al. Low-dose radiation (4 Gy) with/without concurrent chemotherapy is highly effective for relapsed, refractory mantle cell lymphoma.Blood Adv.2019;3(13):2035-2039. doi: 10.1182/bloodadvances.2019030858.