April 2026 Research Update

This month added longer follow-up showing that responses to acalabrutinib (a BTK inhibitor) can be sustained for years in Waldenstrom macroglobulinemia, with important safety issues to keep in view. In a phase 2 study that included both newly treated and previously treated people, response rates stayed high and many patients still had disease control at about 5 years. The same report also documented side effects that matter to patients, including heart-related events and a rare severe bleeding event. [1]

In that study of 106 patients, overall response rates were over 92% in both treatment-naive and relapsed/refractory groups, and major responses were reported in roughly 4 out of 5 patients. Longer-term estimates were also provided, including 66-month progression-free survival of 83.6% in the treatment-naive group and 52.0% in the relapsed/refractory group. This helps put numbers around what "long-term control" looked like in this specific trial population, while still not answering how it compares to other treatments because there was no comparison group. [1]

Safety reporting in the same trial included cardiac events in 20.8% of patients, and there was one treatment-related grade 5 intracranial hematoma. For patients reading research updates, the main point is that longer follow-up can strengthen confidence that a benefit is durable, while also clarifying the types of risks that can show up during extended treatment. [1]

For patients and caregivers, this adds reassurance that acalabrutinib responses observed earlier in the trial did not quickly fade with time, with follow-up extending to about 5 years. It also makes the safety picture more concrete by describing heart-related events and a rare severe bleeding event reported in the study. This evidence may matter now mainly as context for understanding what has been observed with long-term use in one phase 2 study, while details like how it compares against other options remain uncertain because the study did not include a head-to-head comparison. [1]

A small set of reports this month highlighted how the IgM protein in Waldenstrom, and in one case in its precursor IgM MGUS, can sometimes lead to specific complications where the immediate problem is blood thickness or bleeding, and the research focus becomes how to recognize and manage those situations. One report centered on acquired von Willebrand syndrome (a bleeding disorder) occurring with Waldenstrom macroglobulinemia, including a review of prior reported cases. Another report described hyperviscosity syndrome treated with therapeutic plasma exchange in a person with IgM MGUS (a precursor condition), emphasizing special planning when blood products are not an option. [2] [3]

In the acquired von Willebrand syndrome case, bleeding did not improve with a rituximab-based approach and worsened when zanubrutinib (a BTK inhibitor) was added, but the patient reached a complete response with a bortezomib-based regimen. In the same paper's review of 39 reported cases, most reported responses were seen with rituximab-based regimens (18/22) and bortezomib-based regimens (4/5), while BTK inhibitors were reported to worsen bleeding in 3/5 cases. Put simply, this collection of rare cases points to bleeding risk as something that can behave differently depending on the Waldenstrom-directed regimen, although the numbers are small and based on case reports. [2]

In the hyperviscosity case, therapeutic plasma exchange was followed by improvement in blurry vision, a decrease in measured serum viscosity, and improvement in anemia. The authors also proposed closer routine monitoring (every 3 to 6 months rather than 6 to 12 months) and adding iron and clotting-related labs for people pursuing bloodless medicine, to try to anticipate complications earlier. This is an example of care planning driven by a patient's specific constraints, rather than a finding that applies to most people with IgM MGUS or Waldenstrom macroglobulinemia. [3]

For patients, these reports are most useful for understanding that Waldenstrom (and sometimes IgM MGUS) can affect the blood in different ways, including making it harder to clot or making it thicker, and that these problems may be handled with targeted approaches such as plasma exchange or changes in the Waldenstrom regimen. The evidence here is mainly from individual cases and small collections of cases, so it cannot tell how often these complications happen or which approach works best for most people. What it does add this month is clearer real-world examples of how bleeding can worsen with a BTK inhibitor in this setting, and how monitoring and planning may look when transfusions or blood products are not acceptable. [2] [3]

This month also included case reports reminding readers that Waldenstrom macroglobulinemia can be discovered in unexpected ways, either through unusual tissue involvement or through an abnormal lab process that prompts deeper testing. The shared message is that diagnosis sometimes depends on putting laboratory findings together with clinical context, especially when the first clue is not a classic symptom. These reports do not change what is known about typical Waldenstrom, but they broaden the picture of how it can first come to attention. [4] [5]

One report described Waldenstrom being diagnosed after an abnormal biochemical result triggered extra lab investigation, including noticing turbid (cloudy) serum and then detecting an M protein using immunoglobulin testing and serum protein electrophoresis. The main point for patients is that sometimes a diagnosis starts from a lab "oddity," and careful follow-up testing can uncover an underlying blood cancer that was not previously suspected. [4]

Another report described very rare involvement of the uterus (myometrium and cervix) by lymphoplasmacytic lymphoma/Waldenstrom, with IgM kappa paraprotein and a MYD88 p.L265P mutation supporting the diagnosis, later confirmed with a bone marrow biopsy. Symptoms included abnormal uterine bleeding and pelvic pressure even though a transvaginal ultrasound was unremarkable. For patients, this illustrates that when Waldenstrom shows up outside the bone marrow, it may look like a problem in another organ first, and diagnosis can require combining tissue findings with blood and genetic tests. [5]

For patients and caregivers, these cases mainly add understanding rather than changing anything about usual monitoring or treatment. They show that unexpected lab findings can sometimes be the first sign that leads to M protein testing, and that very uncommon organ involvement can cause symptoms that initially seem unrelated to a blood condition. Because these are single-patient reports, it remains uncertain how often these situations occur, but they provide concrete examples of the kinds of diagnostic "paths" that can happen in real life. [4] [5]