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There are many different treatment options available for WM patients, and their numbers are increasing as researchers discover more about the biology and genetics of the disease.

Treatment may consist of just one drug (single-agent therapy), or two or more drugs (combination therapy).  Most studies seem to indicate that combination therapies are more effective, resulting in better and/or longer-lasting responses.

Treatment can usually be administered in an outpatient setting or at home.  It may be oral, by intramuscular or subcutaneous injection, or by intravenous therapy.  Some treatments require that certain medications be taken the day before or the day of treatment in order to minimize associated side effects.

Treatment cycles may take several weeks to months, depending on the course of therapy chosen. It is not unusual to have a round of therapy and then wait a week or a month before another round of treatment, although some of the newer oral therapies require daily dosing instead on an on-going/steady state basis. Hematologist-oncologists follow established protocols for treatment but may make adjustments depending on side effects or response to therapy.

Most of the treatments in use today were originally approved for the related cancers of follicular lymphoma, chronic lymphocytic leukemia, and multiple myeloma.  Once additional Phase 1 and Phase 2 clinical trials established that these treatments had both an acceptable safety profile and were effective for WM patients as well, they were prescribed for “off label” use in WM.

The standard first-line treatment protocol (i.e., the typical first treatment for a WM patient) in Canada, across all provinces, is currently Bendamustine plus Rituximab.  But all WMers are unique and different.  Your oncologist may recommend other approaches, based on your individual symptoms and circumstances.  Below, we provide:

  • an overview of the breadth of treatments available today for WM,
  • a few words about the class of drugs known as BTK inhibitors, and their status in Canada, and
  • a pointer to information about CAR-T therapies.

More information can be obtained by visiting the various subsections in Education on our website.

Download your own copy of a booklet entitled Essential Information: A Physician’s Guide.  In partnership with the IWMF, this booklet is part of a global initiative to educate patients and doctors, worldwide.  It is a compilation of current knowledge on the diagnosis, treatment and established protocols for WM, intended as a guide to physicians.  Although more medically written, we feel it is critical for all patients to be aware of and understand their own treatment options.  Its authors are two WM specialist MDs from the Bing Center for WM, at the Dana-Farber Cancer Institute.

BTK inhibitors are daily oral drugs that target the Bruton’s tyrosine kinase (BTK) pathway in B-cell growth and development.

With the exception of Bendamustine + Rituximab (BR), no other drug therapy routinely gives such long remissions.  BTK inhibitors are typically less toxic than BR, and the newer-generation of BTK inhibitors improve on the older ones, although they have not been studied as long.  However, BTK inhibitors are “forever drugs”, in that one takes them until there is disease progression or drug toxicity.  And with that comes a much, much higher cost, whether to the medical system or to the patient.

In the Canadian context, the following BTK inhibitors are visible:

  • Imbruvica (ibrutinib) by Janssen.  This was the first BTK inhibitor, and the first drug specifically designated for the treatment of WM, approved by the US FDA in 2015.  It has since been approved by Health Canada for the treatment of WM.
  • Brukinsa (zanubrutinib) by Beigene.  This was approved in May 2021 by Health Canada for the treatment of WM.
  • Calquence (acalabrutinib) by Astra Zeneca.  This has been approved by Health Canada for CLL but is also in a WM clinical trial across Canada.  See our coverage of the BRAWM trial.
  • Pirtobrutinib (formerly Loxo-305) by Loxo Oncology.  This drug is in clinical trials in the US.  It is in a new class of BTK inhibitors known as “non-covalent” BTK inhibitors.  Importantly, it has shown that it can be effective even after patients have relapsed on Ibrutinib.  These trials are open to suitable Canadian WM patients.  However, costs for Canadians to participate in US clinical trials vary widely, by site.  For more information on participating in a US trial, as a Canadian, contact us.  Also, see one member’s experience in such a trial.
  • Nemtabrutinib (formerly ARQ 531 and MK-1026) by Merck.  This drug is in clinical trials in the US and in Canada (see our coverage).  It is another member of the class of non-covalent BTK inhibitors.

The status of funding for BTK inhibitors by the provinces is mixed — at this point (mid-2023), some do and some do not.  Provinces do have the option of granting patients Compassionate Access to these drugs under specific conditions.  See more discussion of paying for BTK inhibitors in our list of Common Canadian Questions.  The cost of the treatment should never be a barrier if it is the best option for you.

One of the more exciting developments is CAR T-cell therapy, which is being used, successfully, on WM patients in clinical trials and is considered to be potentially curative.  There are, however, very few of those clinical trials in Canada.

CAR-T therapy involves taking a patient’s T cells, performing genetic engineering on them.  That engineering gives the T cells new receptors, which allows those T cells to target a specific molecule typically present on the surface of a specific type of cancer cell.  The new receptors are called chimeric antigen receptors (CARs) and thus (since we are dealing with T-cells), we have CAR-T therapy.  Scientists harvest T cells from people, genetically alter them, multiply them, then infuse the resulting collection of CAR T cells into patients to attack their tumors.

As noted above, the use of CAR-T therapy for WM is still at the clinical trial stage, and rare.  The Princess Margaret Hospital in Toronto has developed an 8-part video course for patients thinking about CAR-T therapy.  If you are contemplating CAR-T, or it has been mentioned to you by your medical team, this set of videos may be of value.

Also, see our post at CAR T-cell Progress in Canada for more information and links about CAR-T therapies.

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This was Paul’s 2021 walk:

Many thanks to ESRI Canada for supplying this dashboard so we can track Paul’s progress!
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