Home Lymphoma New Treatments for Lymphoma, Leukemia Unveiled at Cancer Conference

New Treatments for Lymphoma, Leukemia Unveiled at Cancer Conference

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Encouraging news on cancer treatments such as CAR-T therapy and monoclonal antibodies was announced at an annual conference. Luis Alvarez/Getty Images
  • Updates on treatments for blood cancers such as leukemia and lymphoma were presented at the annual conference of the American Society of Hematology.
  • Scientists reported on further advancements in CAR-T therapies that boost a person’s immune system to fight cancers.
  • There were also reports of promising results of drugs known as monoclonal antibodies.

Every December, the American Society of Hematology (ASH) holds its Annual Meeting and Exposition.

The confab typically attracts physicians, scientists, biopharmaceutical executives, patient advocates, patients, media, and others from around the globe.

They take planes, trains, cars, and bicycles to share their latest findings in the treatment of blood cancers and other blood diseases.

Some years it’s held in San Diego, California. Other years, in Florida.

This year? On a computer, of course.

More than 30,000 participants from 117 countries attended the online platform. That’s an all-time record.

Among the most newsworthy elements of this year’s meeting was the quality and quantity of clinical trials for next-generation treatments for people with lymphoma, leukemia, and other blood cancers.

The technologically oriented treatment modalities include chimeric antigen receptors (CAR-T), bispecific antibodies, cellular therapies, gene therapies, targeted therapies, combination therapies, and natural killer cell therapies.

Here’s some news from the conference.

To “T,” or not to “T,” that is the question.

No, it’s not the pensive soliloquy from William Shakespeare’s “Hamlet.”

It’s the equally profound question people with lymphoma and leukemia are asking themselves and their doctors.

CAR-T cell immunotherapy, which programs the body’s T cells to attack cancer, works well for many people with blood cancer.

It’s providing long remissions and even perhaps a cure in some cases.

But there are some concerns about CAR-T’s side effects.

Scientists are working to mitigate and ideally eliminate the potentially severe side effects of CAR-T.

But they’re giving some people and physicians pause.

To “make” CAR-T cells, a sample of a person’s T cells are taken from the blood and engineered so that special structures called chimeric antigen receptors are on their surface.

When these cells are reinjected into the person, the receptors help the T cells identify and attack cancer cells throughout the body.

Hundreds of CAR-T clinical trials are underway. Three separate CAR-T treatments for lymphomas and leukemias are on the market with more waiting in the wings.

CAR T-cell therapy has targeted such blood cancers as follicular non-Hodgkin’s lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, acute lymphoblastic leukemia, multiple myeloma, and chronic lymphocytic leukemia.

Companies entering the space in recent years include bluebird bio, Cellectis S.A., Janssen Pharmaceuticals, Kite Pharma, Legend Biotech, Novartis, and Pfizer.

In a phase 2 clinical trial presented at ASH, the drug Kymriah, a CAR-T from Novartis that’s already approved for diffuse large B-cell lymphoma and pediatric acute lymphoblastic leukemia, provided 65 percent of people with previously treated follicular non-Hodgkin’s lymphoma a complete remission.

Follicular lymphoma, the second most common form of non-Hodgkin’s lymphoma, is still considered to be incurable. The cancer typically returns.

With each treatment, the cancer becomes more difficult to eradicate.

Dr. Nathan H. Fowler, a physician in the department of lymphoma and myeloma in the division of cancer medicine at MD Anderson Cancer Center in Texas, said in a press statement that he was encouraged by these interim results.

“There is a great need for potentially definitive options and an alternative to stem cell transplant,” Fowler said. “We look forward to continuing to learn more about how Kymriah may provide benefit for these patients.”

Despite such positive results, CAR-T can be problematic.

The CAR T-cell therapy success rate is about 30 to 40 percent for lasting remission, with no additional treatment, according to Dr. Michael R. Bishop, the director of UChicago Medicine’s cellular therapy program.

But some cancers do fall back out of remission after treatment.

And some people have serious side effects, including neurotoxicity and severe cytokine release syndrome, a dangerous and sometimes fatal immune system overreaction.

Significantly, in the trial of Kymriah for follicular non-Hodgkin’s lymphoma, no participants experienced severe cytokine release syndrome.

Other CAR-T trials, too, are reporting fewer toxic responses in participants.

“Novartis is dedicated to continuing to explore the safety and efficacy of Kymriah for patients with advanced blood cancers who do not achieve long-term remissions despite multiple prior lines of therapy,” Dr. John Tsai, the head of global drug development and chief medical officer for Novartis, said in a press statement.

Meanwhile, other novel therapies have shown the potential to be viable alternatives for cancers that can’t or won’t be treated with CAR-T.

One of the newest modalities scientists are touting is bispecific antibodies.

Bispecific monoclonal antibodies are artificial proteins that can simultaneously bind to two different types of antigen.

An antigen is a molecule or molecules that can be bound by an antigen-specific antibody or B cell antigen receptor.

Bispecific antibodies are a fast-growing part of the cancer immunotherapy landscape.

One of those bispecific antibodies, odronextamab, is showing positive results in relapsed/refractory non-Hodgkin’s lymphoma, including in people who have previously received CAR-T.

Odronextamab is from Regeneron, which has studied antibodies for years and has several similar treatments in trials.

Regeneron is best known now for REGN-COV2, the COVID-19 antibody cocktail that was used to treat President Donald Trump in early October.

The Food and Drug Administration (FDA) granted emergency use authorization to REGN-COV2 on Nov. 21.

L. Andres Sirulnik, a senior vice president at Regeneron, told Healthline that the company’s phase 1 study of odronextamab demonstrated potentially “best-in-class” clinical results for people with relapsed follicular non-Hodgkin’s lymphoma, diffuse large B-cell lymphoma, and other B-cell non-Hodgkin’s lymphomas.

“What makes this bispecific antibody special is its ability to activate the patient’s own T cells through the CD3 pathway and bridge them to cancer cells for targeted killing,” Sirulnik said.

“Our bispecifics may prove to benefit patients with already rapidly progressing disease because, in addition to being an off-the-shelf option, we can also readily adjust their dose according to the patient’s tolerability for the drug,” he added.

Sirulnik noted that this treatment is “an important alternative to CAR T-cell therapy, which does not possess the same flexibility to be dose-adjusted, and because the time for patient-specific development may not be ideal for patients with rapidly progressing disease.”

He added that unlike CAR-T, “bispecifics do not require a chemotherapy conditioning regimen.”

So-called costimulatory bispecifics is another area of focus for Regeneron, he said.

“Our next generation of bispecifics will be looking at maintaining the initial signal given by CD3 by engaging CD28 as a costimulatory signal,” Sirulnik said.

“In a simple analogy: We now have bispecifics targeting CD3, the T cell ignition switch, combined with bispecifics targeting CD28, the T cell gas pedal,” he said.

“By combining the two, we expect to enhance and sustain the patient’s T cell responses to increase the number of patients responsive to therapy and provide longer lasting remission,” Sirulnik said.

Another rising star in the blood cancer world is targeted therapy.

Currently, the 5-year survival rate for adults with acute myeloid leukemia is 28.7 percent.

New data from Kura Oncology, a San Diego-based biotech company, shows that KO-539, its genetically targeted menin inhibitor, can effectively treat acute myeloid leukemia.

“Despite the recent approval of multiple new treatments for acute myeloid leukemia, the outcomes of these patients remain dismal and represent an urgent unmet need,” Troy Wilson, PhD, Kura’s co-founder and CEO, told Healthline.

“We are highly encouraged by the preliminary first-in-human data for our menin inhibitor, KO-539, for the treatment of patients with relapsed or refractory [acute myeloid leukemia],” he said.

For acute myeloid leukemia to persist, the leukemic blast cells have to remain in a perpetual, undifferentiated state, and they have to proliferate.

Wilson explained that KO-539 shuts off the expression of certain genes that maintain the leukemic blast cells in an immortal, undifferentiated state.

When a person is treated with this drug, Wilson explained, the cells either undergo apoptosis, also known as programmed cell death, or they differentiate into mature cells, live a few weeks, and then die off.

“When the cells die off, the patient may have a complete remission,” Wilson said.

“Those cells don’t come back because they have differentiated into mature cells. That’s a one-way trip, so the responses have the potential to be very durable,” he added.

In the pharmaceutical world, the big fish often swallow up the smaller fish.

In November, Merck, one of the biggest fish in the pond, announced it was purchasing VelosBio, a private startup, for $2.75 billion.

The purchase took effect the day after VelosBio revealed its latest data to ASH.

VelosBio officials said their antibody drug conjugate, VLS-101, demonstrated durable responses in people with advanced mantle cell lymphoma or diffuse large B-cell lymphoma, including those who received prior therapies, including CAR-T and stem cell transplantation.

Antibody drug conjugates are targeted drugs that combine monoclonal antibodies specific to surface antigens present on particular tumor cells with toxic anticancer agents linked.

The VLS-101 antibody is linked to a toxic agent called monomethyl auristatin E.

After the antibody binds to ROR1 antigen on the cancer cells, the antibody is designed to enter those cells and release the toxin to destroy the cancer cells.

In mouse models of human hematologic malignancies and solid tumors, VLS-101 showed robust antitumor activity.

In late August, the FDA granted VLS-101 orphan drug and fast track designations for the treatment of mantle cell lymphoma.

Dr. Thomas Kipps is an internationally known expert on cancer research, immunology, and gene therapy as well as deputy director of research operations at the University of California, San Diego Moores Cancer Center.

Kipps said he has been studying this mechanism in the lab for 15 years and discovered its possibilities.

Kipps told Healthline that VLS-101 is showing “tremendous responses in lymphomas and has potential to treat solid tumor cancers as well.”

Kipps explained that the antibody latches onto ROR1, a protein that can be found on the surface of a variety of cancer cells.

“Once the antibody gets absorbed into the cancer cell, the toxin it’s attached to kills the cell,” he said. “It’s a clean process with little interference. The potential for this treatment is vast.”

Among the 117 countries that had a presence at ASH was China, whose biotech industry and, specifically blood cancer sector, are booming.

JW Therapeutics, a leading clinical stage cell therapy company based in Shanghai, presented data at ASH from its study of the RELIANCE Trial of relmacabtagene autoleucel (relma-cel).

The RELIANCE Trial was the first study of a CAR-T therapy manufactured in China for the treatment of relapsed or refractory B-cell non-Hodgkin’s lymphoma.

According to a press statement, “relma-cel shows similar efficacy while providing the potential for an improved toxicity profile in heavily pre-treated patients with r/r LBCL of poor risk features.”

Dr. James Li, the co-founder, CEO, and chairman of JW Therapeutics, said in the press statement, “The presentation reinforced relma-cel’s significant competitive advantage in the CAR-T market in China, highlighting its competitive efficacy and safety profiles.”

“We are confident that these data will provide strong support to relma-cel’s ongoing New Drug Application (NDA) in China and we look forward to bringing this innovative CAR-T therapy to patients as soon as possible,” he added.

BeiGene, an international pharmaceutical company founded in Beijing, is the first China biotech company to have a cancer drug approved in the United States.

BeiGene, which now has a large presence in the United States, has ascended the lymphoma and leukemia treatment ladder.

One of BeiGene’s leading treatments is Brukinsa, a selective inhibitor of Bruton’s tyrosine kinase that works by blocking unusual activity associated with malignant B-cell growth and survival.

In one of the latest BeiGene trials, company officials said Brukinsa was shown to be highly active in people with relapsed/refractory marginal zone lymphoma in initial results from the phase 2 MAGNOLIA clinical trial.

Dr. Jane Huang, the chief medical officer of hematology at BeiGene, told Healthline that the initial results of the trial included a high overall response rate of 74 percent and a well-tolerated safety profile.

“Together with the head-to-head ASPEN trial data, which demonstrated Brukinsa’s safety advantages over ibrutinib, this confirmed the preclinical hypothesis that a BTK inhibitor designed to minimize off-target effects will enable improved tolerability in patients,” she said.

“Safety is likely able to be extrapolated to different tumor types, and the important thing is that we see consistency in the safety data over and over again,” she added.

More specifically in indolent lymphomas, complete responses can confer long-term patient benefit, Huang explained.

The median follow-up time being 10.7 months, “we’re seeing really encouraging results across all subtypes, and we look forward to reporting follow-up results as the data mature,” she said.

Huang added, “Our hope is that we can offer patients, particularly those with higher risks, a treatment that will help them in their fight against the disease.”

https://www.healthline.com/health-news/new-treatments-for-lymphoma-leukemia-unveiled-at-cancer-conference

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