At this year’s ASH we are presenting the long-term outcome of our study which is to use this novel combination of lenalidomide, a pill,and also rituximab which is an anti-CD20 antibody to treat as initial treatment for patients with mantle cell lymphoma. As we reported in 2015 for the interim report, that combination has very high response rates. The overall response rate was over 90% and complete remission was over 60%. It would be nice to see if those responses are durable so at this year’s ASH we are pleased and able to present those long-term outcomes. It does seem to be the case, at the four year mark 70% of the patients continued to stay in durable remission and 83% of the patients are alive and doing well. Additional to response duration we also reported safety long-term data which is also very important. We did not see any new safety signals and, as we reported earlier, the treatment is generally well tolerated and certainly we see cytopenias, which is reduced blood counts, they were generally asymptomatic. Things like febrile neutropenia were very rare. We also observed constitutional symptoms, inflammatory symptoms, at the very early stage of the induction. Those were generally reduced in frequency and severity as time goes by. Patients would normally receive an induction phase which lasted for twelve cycles and this is followed by maintenance treatment which would be ongoing. Patients also had the option to stop treatment after three years on study.
I was reading through some of the adverse events that came up around the 3-4 year mark including the infections that came along. Any thought if that might have been attributable to the low blood cell count?
I think it’s a very fair question. Common infections are being very closely tabulated on the study and they general comprise of upper respiratory, urinary tract infections, sinusitis and skin infections which you may expect to see in this patient population. They are on a form of immunosuppressive therapy with anti-CD20 and also lenalidomide so those are things that we should maintain vigilance. However, all of those are easily managed in outpatient clinic settings and we really would need to get patients into the hospital and getting IV antibiotics. So it’s more so because of the immune suppressed regimen that the blood counts, I would say, all the treatment would have a threshold for a patient to restart their oral medications. So, generally speaking, I don’t think our patients would be on a very prolonged period of low blood counts, in particular neutropenia.
The incidence of secondary malignancies, would you see those as more than you’d expect in this patient population?
Also a very good and fair question. We report secondary malignancy very diligently and the majority of the cases, in our case there were only six subjects that reported secondary malignancy. Four of them are skin based, so limited squamous cell or basal cell, and they were resected and patients were maintained on the treatment. I do want to point out that the study did not preclude patients with a prior history of skin cancer to enrol as long as they did not have any active evidence of disease at the time of enrolment. So our reporting is any occurrence without respect to whether they were related to treatment or not.
On the other hand, patients with a diagnosis of lymphoma and also on chronic immunosuppressive therapy, they are at a high risk of developing those skin malignancies. I do want to report that there were two cases of systemic secondary malignancy that were reported, one was with pancreatic cancer and the other Merkel cell cancer. Both occurred in patients with advanced age and certainly we would advocate for very close vigilance while patients are receiving this chronic therapy, especially with biologics.
When it comes to going beyond this patient group, you’ve said it’s a five year follow-up, are there any observations or ongoing trials for large populations or different age ones?
We sincerely hope that with this long-term data which validates the efficacy but also provides additional information on the safety we would inspire enough interest and also momentum for a larger study to take place, preferably a multi-centre or intergroup global study to look at this particular combination and possibly compare that with other conventional combinations. Another possibility is, as you know, there are new advances in novel therapies with other agents, so new combinations is another promising direction and strategy that one should consider, at least to explore in the pilot setting. So we’re very excited to be part of this ongoing effort to try to bring new treatment to our patients. One would provide higher treatment efficacy, effectiveness, at the same time hoping to provide that in a very patient-friendly environment, outpatient setting, in order to preserve quality of life.
If you had to give a summary statement, a take home message for any clinicians watching this, what would it be?
That novel treatment for a mantle cell lymphoma is on the horizon. That includes using new combinations that are chemotherapy free as initial therapy and our early efforts, or pilot study, has shown that this effort can be active and relatively safe at the same time. However, we hope that more efforts for larger studies with a broad population should be ongoing to test our hypothesis and bring those possibilities closer to reality for our patients.