IWMF Webinar: ASCO 2021 Advances in WM

The International Waldenstrom’s Macroglobulinemia Foundation (IWMF) recently held the latest webinar in its Global Education series on July 9, 2021. This webinar was a summary of research presented at the American Society for Clinical Oncology (ASCO) 2021 meeting, including several studies that focused on Waldenstrom’s macroglobulinemia (WM). The webinar was presented by Dr. Sheeba K. Thomas.

Waldenström’s macroglobulinemia, which is also known as lymphoplasmacytic lymphoma, is a rare type of blood cancer that affects two types of B lymphocytes, including plasma cells and lymphoplasmacytoid cells. A distinct characteristic of this type of cancer is the presence of a high concentration of IgM antibodies. It is a slow-progressing form of blood cancer, and many patients can lead active lives. While it cannot be cured, it is treatable; some patients are able to experience years of remission without symptoms. There are only about 1,500 new cases per year in the U.S. Although it mostly occurs due to sporadic genetic mutations, a family history increases risk. Symptoms include vision loss, headaches, enlargement of the lymph nodes, liver, and spleen, bleeding nose and gums, weight loss, fatigue, and general weakness. To learn more about WM, click here.

A total of eight studies on WM were summarized in the presentation:

  1.  Prognostic impact of depth of response in Waldenström macroglobulinemia patients treated with fixed duration chemoimmunotherapy (Perera, et al.)

This study compared three combination therapies consisting of rituximab alongside either bendamustine, cyclophosphamide + dexamethasone, or bortezomib + dexamethasone. The researchers were hoping to determine if the quality of response at six months had impacts on overall survival (OS), progression-free survival (PFS), and time to next therapy (TTNT). Overall, patients with a major response at six months saw greater PFS, OS, and TTNT.

2. Cost‐effectiveness of zanubrutinib versus ibrutinib in adult patients with Waldenström
macroglobulinemia in the United States (Castillo, et al.)

In comparing the costs of these two drugs, the results were very comparable overall; zanubrutinib was more expensive, but this was mostly because patients used the drug longer before experiencing treatment failure. The drug also had lower routine care and terminal care costs compared to ibrutinib.

3. Efficacy and safety of zanubrutinib versus rituximab‐based chemoimmunotherapy in Waldenström macroglobulinemia (WM): Matching‐adjusted indirect comparisons

This study evaluated match adjusted comparisons of zanubrutinib vs rituximab + cyclophosphamide + dexamethasone and rituximab + bendamustine. Overall zanubrutinib demonstrated greater OS and PFS.

4. Preliminary results of the phase 2 study of zanubrutinib in patients with previously treated B‐cell malignancies intolerant to ibrutinib and/or acalabrutinib (Shadman, et al.)

This trial sought to determine if patients would have a different safety profile to zanubrutinib after being treated with ibrutinib or acalabrutinb. These therapies are all of the BTK inhibitor class. The researchers were looking for the return of previous side effects or new side effects. While some patients had to adjust their dose or saw treatment interruptions, only a small number saw the same side effects that caused intolerance on the earlier drugs come back after switching.

5. Updated results of the selective Bruton tyrosine kinase (BTK) inhibitor TG‐1701, as monotherapy, and in combination with ublituximab and umbralisib (U2) in patients (pts) with B‐cell malignancies (Cheah, et al.)

In WM, monotherapy produced an overall response rate (ORR) of 95 percent. The combination treatment produced an ORR of 79 percent and a complete response (CR) of 21 percent.

6. First‐in‐human study of lisaftoclax (APG‐2575), a novel BCL‐2 inhibitor (BCL‐2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs) (Ailawahdi, et al.)

Lisaftoclax appears to have a better side effect profile than other BCL-2 inhibitors. Compared to other cancers, WM also had one of the longest treatment durations, suggesting that patients saw benefit and tolerance for longer.

7. Treatment Free Remission (TFR) and Overall Response Rate (ORR) Results in Patients with Relapsed/Refractory Waldenstrom’s Macroglobulinemia (WM) Treated with CLR 131 (Ailawahdi, et al.)

The treatment appeared to elicit a response in all patient subtypes. Patients have experienced over 13 months of ongoing treatment-free remission. The safety profile of the treatment was also well tolerated.

8. Real‐world treatment patterns, adherence, costs, and healthcare resource utilization associated with Waldenström macroglobulinemia in the United States (Yang, et al.)

This study found that costs per patient per month rose steadily the more courses of treatment they received:

1st line chemo: $18,682

3rd line chemo: $36,878

Click here to watch a recording of the webinar.

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