Are Follicular Non-Hodgkin’s Lymphoma Patients Finally Getting Newer, Better Options to Treat Their Cancer?

It’s been nearly 23 years since I participated in a clinical trial after my follicular non-Hodgkin’s lymphoma recurred. When I was initially diagnosed with stage IV Follicular (FL) in early 1997, I went through five rounds of CHOP chemotherapy - cyclophosphamide, doxorubicin, vincristine and prednisone. It gave me two and 1/2 years of remission. But the treatment was rough.

When the cancer returned, instead of doing chemo again I chose to enroll in a clinical trial of a radio-immunotherapy (RIT) called Bexxar. I did my homework on the trial, and I then respectfully told my oncologist that this was my decision. He tried to talk me out of it. But I was resolute. 

 

Ultimately, my choice proved to be the right one. Multiple oncologists tell me that I am now cured of my follicular non-Hodgkin’s lymphoma. Despite the fact that many of my fellow patients were cured by Bexxar, the drug is no longer on the market for reasons that have absolutely nothing to do with its efficacy or safety.

 

Ever since Glaxo Smith Kline shelved Bexxar, as I wrote about here , and here, I've been on a mission to help my fellow follicular (FL) patients find newer, better options to treat their cancer.

 

I've worked with several dedicated, forward-thinking pharmaceutical companies to promote and encourage the study of new treatments for follicular NHL. It is desperately needed. 

But the research has been slow sledding. Follicular lymphoma, the second most common form of non-Hodgkin's lymphoma, remains an often relentless type of cancer that for many patients brings multiple relapses.

 

Since Rituxan was approved by the Food and Drug Administration (FDA) to treat follicular lymphoma in 1997, we've not seen too much movement in terms of challenging the standard of care for this horrible disease, or finding truly effective alternatives after patients recur. 

But at this month's American Society of Hematology (ASH) Annual Meeting, the largest gathering of blood cancer oncologists and scientists in the world, a boatload of promising trial data was presented from a variety of newer-generation medicines for follicular.

Viable new options are emerging at rapid pace. My hope and expectation is that some of these newer options will eventually replace the current standard of care and become first-line therapies. 

Below are just a few of the many treatments being studied that have great potential:

 

A Cell-Signal Blocker Emerges

One of the most interesting and potentially effective new drug technologies for follicular lymphoma is zandelisib. Previously called ME-401, zandelisib, from MEI Pharma in San Diego, is neither a chemotherapy nor a CAR T-cell immunotherapy nor a bispecific antibody.

Zandelisib is a cell-signal blocker. That simply means that it targets a protein in the body called P13K, which plays a key role in the growth and survival of the type of white blood cells that become abnormal in B-cell lymphomas. 

 

Blocking PI3K can help stop lymphoma cells from dividing or cause the cells to die.

MEI Pharma and Kyowa Kirin recently announced data from the Phase 2 TIDAL clinical trial of zandelisib in patients with relapsed or refractory follicular lymphoma.

In the trial, zandelisib showed a 70.3 percent objective response rate and 35.2 percent of patients achieved a complete response. And fewer than ten percent of the trial participants discontinued therapy due to side effects.

 

In an exclusive interview with The Reno Dispatch, Dan Gold, CEO at MEI Pharma and a gifted scientist who's been working in the lymphoma sector for many years, explained the status of this promising treatment. 

 

“We are very excited by the emerging zandelisib data, which indicate the potential to positively impact the standard-of-care for patients with relapsed or refractory follicular lymphoma," he said. 

 

"Once we have collected the final data from the follicular lymphoma patient cohort, we intend to discuss our plans to submit an accelerated approval marketing application with the FDA.” 

 

Gold added, "Our development efforts with our partner, Kyowa Kirin, to expand the utility of zandelisib include the ongoing Phase 3 COASTAL study evaluating zandelisib plus rituximab [Rituxan] in patients with relapsed or refractory follicular or marginal zone lymphomas.”

Bispecific Antibodies

 

But zandelisib is far from alone. There are multiple new treatments and modalities for FL that are showing very positive numbers in trials, including Roche’s Mosun.

 

In a clinical trial presented at ASH, Mosun, a bispecific antibody that redirects T cells to eliminate malignant B cells, induced "deep and durable remissions" in follicular NHL patients, including those with double-refractory disease.

 

"Notable updates coming out of ASH 2021 include experimental bispecifics such as mosunetuzumab [Mosun], which induced high response rates and durable responses for patients with relapsed/refractory follicular lymphoma,” Lee Greenberger, chief science officer at the Leukemia Society, told The Reno Dispatch.

“With a response rate of 70%, a complete response rate of 54%, and a median duration of response of 23 months, this could be a valuable addition to the treatment landscape in follicular lymphoma,"he said.

Greenberger added that Genentech's glofitamab, another bispecific for the treatment of relapsed or refractory follicular lymphoma, also showed significant response rates with good durability. 

"Bispecific antibodies offer the advantage of an off-the-shelf therapy with a performance that appears to be competitive compared to currently approved CAR T therapy for relapsed or refractory follicular lymphoma," he said. 

CAR T-Cell Immunotherapies

Not to be outdone, CAR T-cell immunotherapies, which have been the talk of the cancer research world for the last several years, are also making a strong statement about their place in the follicular space. 

 

Last March, the FDA granted Yescarta, a CAR T from Kite, a Gilead company, "accelerated approval" as a third-line therapy for adults with relapsed or refractory follicular. Yescarta, continued to shine at ASH this month, as did Kymriah, a Novartis CAR T product.

 

Both will likely challenge other drugs for third-line treatment, and eventually could become the new standard of care for FL and other types of lymphoma. 

The other good news about CAR T is that scientists continue to make progress in reducing cytokine release syndrome, the serious and sometimes even fatal side effect of this groundbreaking treatment.

 

Perhaps the most exciting piece of data in the Kymriah report presented at ASH is that no high-grade cytokine release syndrome was reported within eight weeks post-infusion and no new safety signals were identified.

"The ability to administer Kymriah, a potentially definitive treatment, in the outpatient setting may reduce the burden of therapy for patients and their care teams," Jeff Legos, global head of oncology & hematology development at Novartis, said in a press statement. 

"The breadth of follicular lymphoma data presented at this year's ASH demonstrate the potential for Kymriah to provide transformative results and a positive impact on health systems overall."