There are no treatments that can cure WM, although in most cases the disease is indolent (slow growing) and can be effectively managed with appropriate therapies.
Overview of Treatments
There are many different treatment options available for WM patients, and they 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. 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. And at the bottom of the page, there are a few words about the class of drugs known as BTK inhibitors, and their status in Canada.
More information can be obtained by visiting the various subsections in Education on our website.
Treatment options for Waldenstrom’s macroglobulinemia may include the following:
A few words about BTK Inhibitors
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.
Note that none of these BTK inhibitors are generally funded for WM by the provinces. But 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.