Monjuvi-Revlimid Combination Approval Fills Unmet Need for Certain Patients with DLBCL

The combination of Monjuvi (tafasitamab-cxix) and Revlimid (lenalidomide) fills an unmet need for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) unable to undergo autologous stem cell transplant, said Dr. Gilles Salles.

Recently, the FDA approved Monjuvi-Revlimid for adult patients with relapsed or refractory DLBCL including DLBCL arising from low grade lymphoma and are not eligible for autologous stem cell transplant. The approval was based on results of the single-arm phase 2 L-MIND study which achieved a 55% overall response rate in patients, with 37% of patients reaching a complete response and 18% reaching a partial response.

The study’s lead researcher Dr. Gilles Salles, head of the hematology department of the Centre Hospitalier Lyon-Saud in France, spoke with CURE® and discussed how the treatment works in patients and what need it fills for this patient population.

CURE®: How does the therapy fit an unmet need for this patient population?

Salles: Diffuse large B-cell lymphoma is the most common lymphoma subtype. It's an aggressive disease which involves lymph nodes, organs and bone marrow. While we have made progress in the past with this disease with chemotherapy and antic-20 antibodies, we have about 30 to 40% of patients that may not respond or relapse after the standard of care.

Some of these patients can receive an analogous stem cell transplant. But unfortunately, because of the age of patients suffering from diffuse large B-cell lymphoma, because some of them carry some comorbidities, or because some patient failed to go to the path of autologous stem cell transplant, we have a population of patients which is consistent and evaluated at about 10,000 patients per year in the United States that are non-transplant eligible and in the relapsed refractory setting with a diffuse large B-cell lymphoma. For these patients, what we do usually is we deliver again, some form of cytotoxic classical chemotherapy, but the tolerability of this agent is not extremely good.

They have already received chemotherapy, as mentioned some of them are elderly or have commodities, and you can see of this second line chemotherapy, when this is not fitted in perspective of autologous stem cell transplant is essentially palliative. So, there is a real unmet need for those patients that are non-transplant eligible with diffuse large B-cell lymphoma that had failed primary therapy. The research that was done in science many years was clearly to try to find the other form of immune based therapy that will perhaps target different antigen on the tumor cells. And among these antigens, CD19 had appeared quite promising because this is the antigen that has been chosen also for the new treatments such as CAR-T cell treatment by an antibody drug conjugates in development and the drug we will be talking about tafasitamab (Monjuvi).

How would you explain to patients how this would work for them? What are some key highlights they should know about?

For the patients, I think, they should know that this is a novel form of therapy, where we combine agents that are aiming to fight against a tumor and eventually destroy it and make it disappear. And this is specific for the tumor because the antibodies specifically recognize the tumor cell and does not attack normal organs.

The lenalidomide, which is an adjunct to Monjuvi will reinforce this activity and reinforce the ability of immune cells to fight against the tumor. So, it's really a combination that is mobilizing the immune system to fight against lymphoma, with the hopes that it will be disappearing, and that they achieve complete response to therapy.

How do these therapies work in tandem with one another? How does this work for patients?

Yes, I think this is important to know. Again, this is an immunotherapy. So, it's really a normal cytotoxic classical therapy, and the antibody tafasitamab (Monjuvi) here is delivered as an intravenous infusion, initially every week, then every two weeks and continuing until as long as the disease is controlled. Lenalidomide is an oral agent, which is taken orally three weeks out of four in combination to Monjuvi. So, when the drug is infused, it's usually well tolerated, a few patients that may have some side effects related to infusion. Like all patients that receive an infusion of biotherapy and immune based therapy and antibody.

There are some patients that have a little bit of chills, modification in blood pressures, little bit of fever, but this is usually resolved within 12 to 24 hours. And it can be really given as an outpatient treatment, patients don't have to be hospitalized for several days or to be inpatients to receive this therapy. And as long as the disease is controlled, improving and things like that, this regimen is really delivered as an ambulatory regimen for a longer period.

Can you expand on some of the side effects associated with this treatment?

Yes, I think there are some side effect as unfortunately many other therapies in cancer. Here's the side effects that we see are essentially a decrease of normal blood cells, which includes the white blood cells, the platelets and sometimes, but less frequently, the red cell. So, the white blood cells are decreasing in about half of the patients and this may increase the susceptibility of patients to infections.

Hopefully, we have seen that only about 10% or so of the patients have really developed infections that needed the additional care which will be quite serious. Similarly, I think the dropping platelets may increase the risk of bleeding and we may have to require, but this is only for very few patients, platinum transfusion support. What is important to notice is that the side effect is in, respectively, 50% and 80% of the patients.

If you take over one year, it's one or two episodes per patients but it's not like constant or repeatedly and things like that. So, they appear but they're not that frequent I will say or not hampering the life. That all the side effects which are probably linked also to the use of lenalidomide. So, some gastrointestinal symptoms, bowel control or nausea, things like that, there is a little bit of fatigue linked with that. But I will say that in general on despite the fact that we don't have head to head comparison, this kind of regimen is much better tolerated than classical cytotoxic chemotherapy.