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Expert Explains Latest Advances in Hodgkin Lymphoma, MCL

Also known as high-grade lymphoma, MCL is a type of B-cell NHL. It is an aggressive form of lymphoma that derives from the cells originating in the “mantle zone” and usually affects the bone marrow and gastrointestinal tract.

 Expert Explains Latest Advances in Hodgkin Lymphoma, MCL

Lymphoma is a cancer of the lymph nodes and lymphatic system. The two main types are Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). The main difference between the two is in the specific lymphocyte each involves.

Generally, a physician can determine the difference between HL and NHL by studying the lymphoma cells under a microscope. If he or she detects an abnormal cell known as a Reed-Sternberg cell, the lymphoma is labeled as HL. If, however, the Reed-Sternberg cell is not present, the lymphoma is labeled as NHL.

There are many different subtypes of lymphoma and one in particular is mantle cell lymphoma (MCL). Also known as high-grade lymphomas, MCL is a type of B-cell NHL (out of 70 different subtypes). It is an aggressive form of lymphoma that derives from the cells originating in the “mantle zone” and usually affects the bone marrow and gastrointestinal tract. In the United States alone, MCL accounts for around 6% of all NHL cases.  

Most recently, new treatment options have been added to the paradigms of HL and MCL, thus leading to a more personalized therapeutic approach in clinical practice, as well as improved outcomes.  

Fitting into the treatment paradigm

According to findings from the phase III ECHELON-1 study, a combined brentuximab vedotin regime demonstrated significantly high progression-free survival rate results, in comparison with standard ABVD chemotherapy in 1300 randomized patients with HL. The new regime involved a combination of brentuximab vedotin, vinblastine, doxorubicin, and dacarbazine (AVD). “We know that in patients with previously untreated Hodgkin lymphoma, up to 40% of them will be refractory or will relapse to their initial therapy. Therefore, better induction regimens are necessary” said Chaitra S. Ujjani, a hematologist/oncologist at Seattle Cancer Care Alliance.
Brentuximab vedotin is a well-known antibody-drug conjugate to CD30 and it is already approved by the United States Food and Drug Administration (USFDA) for HL. In this particular study, it was observed that the combined brentuximab vedotin regime lowered the risk of progressive, death or initiation of new treatment by 23% in comparison to that of standard ABVD chemotherapy. The prior endpoint was modified progressive-free survival rate results, with the 82% in the brentuximab arm versus 77% in the ABVD arm over a period of two years. And as a result of the findings, the FDA approved brentuximab for use in combination with chemotherapy as a primary treatment option for adult patients with stage III/IV HL.

Nevertheless, there are still a few areas that remain unexplored when it comes to brentuximab vedotin - one of them being the drug in combination with bendamustine for relapsed patients. In a study published by a group of researchers at Dana-Farber Cancer Institute, it was found that the patients had achieved complete remission under this particular regime, thus allowing them to become qualified to undergo stem cell transplantation.

There has also been interest in brentuximab vedotin in combination with nivolumab (Opdivo) – an immunotherapy agent that is approved in HL. The two have very different mechanisms of action; however, the responses from tested patients were very impressive. “The rationale in combining them was that you could give 2 different types of targeted therapies together and possibly improve outcomes. You could also avoid chemotherapy. The goal is to achieve more personalized treatments” said Ujjani.

Making a significant impact in the MCL space

Moving onto MCL, the potential of BTK inhibitors in relapsed/refractory patients has led researchers to explore ibrutinib in combination with rituximab maintenance therapy in elderly patients with newly diagnosed MCL. “You would want to use BTK inhibitors in the frontline setting, as I said, particularly in the frail and elderly patients. Unlike many new drugs, where they’re first used in a younger and fitter population, BTK inhibitors should be used the other way around” explained Simon Rule, a professor of Hematology at Plymouth University Medical School.

Ibrutinib was approved a few years ago and since then, response rates have been above the 60% mark. While the drug has been associated with unique side effects, researchers are looking into ways to improve this. One of the ways is developing second-generation BTK inhibitors that will hopefully improve the toxicity challenges associated with ibrutinib, including bleeding and bruising. Such an example is acalabrutinib, which has been FDA approved for patients who have had at least 1 prior line of therapy. “Response rates have been very promising; we’re just waiting to see how durable these responses are. The drug also appears to be a little better tolerated. We still see a little bit of bleeding, but nothing significant” said Ujjani.

Looking at other types of biologics is another way to go. BCL-2 plays a role in the pathogenesis of CLL, so it may be able to work in the MCL-setting. Having said that, patients with MCL seem to benefit from venetoclax and in combination with ibrutinib, researchers have observed impressive response rates.

Coming down through the pipeline

There are more MCL1 inhibitors, as well as BTK inhibitors, in the early stages of research and development. However, in terms of their role in MCL, it is too early to tell. The chimeric antigen receptor (CAR) T-cell therapy is another exciting area of research, but its application to this type of lymphoma remains to be determined. “We’re still trying to determine how old a patient should be to safely receive CAR T cells. We have a pretty good hand on how to manage AEs. Once we get a better idea of who can handle this therapy, we will better understand where this fits into treatment” said Ujjani.

When it comes to treating a relapsed/refractory patient with MCL, choosing treatment with acalabrutinib or ibrutinb remains unclear in terms of which one is more effective. Currently, what is known is that acalabrutinib is given twice a day, whereas ibrutinib is given once a day. Patient compliance, as well as associated side effects, should also be taken into consideration. If, for instance, an individual has a high risk of bleeding, it may be best to avoid ibrutinib. That being said, it depends on the individual in question.

Seeing as how multiple different subtypes of lymphoma exist, doctors are using laboratory tests to examine samples of lymphoma cells in order to identify their specific subtype. An accurate diagnosis is a vital part of determining prognosis, as well as receiving proper care. In the meantime, researchers are continuously reviewing different disease courses and treatment choices in an attempt to find a cure for both HL and NHL.

 

References:

  1. https://www.mayoclinic.org/diseases-conditions/hodgkins-lymphoma/expert-answers/lymphoma/faq-20058546
  2. https://www.onclive.com/web-exclusives/expert-explains-latest-advances-in-hodgkin-lymphoma-mcl?p=1
  3. https://www.curetoday.com/articles/novel-combinations-continue-to-shape-mantle-cell-lymphoma-treatment-options
  4. https://www.targetedonc.com/news/btk-inhibitors-will-make-significant-impact-in-mcl-expert-says