June 2026 Research Update

This month added two signals that several non-BTK inhibitor regimens can still control Waldenstrom macroglobulinemia, but the evidence is mostly from non-randomized studies. One report looked at bortezomib-based combinations in people who had already received BTK inhibitors, and another tested obinutuzumab plus bendamustine as a first treatment in a broader indolent lymphoma group that included WM. Taken together, these studies reinforce that responses are possible in different treatment settings, while side effects still need close attention, especially infections and low blood counts. [1] [2]

For people previously exposed to BTK inhibitors, a single-center review of 17 patients reported that bortezomib-based regimens led to responses in most patients, with a median time to best response of 3 months. The study also reported limited nerve damage (neuropathy) and no treatment-related deaths, although some patients had serious low neutrophil or platelet counts. Because the regimens were not all the same and there was no comparison group, this mainly shows what was achievable in routine care rather than proving one best approach. [1]

In newly diagnosed patients, a prospective multicenter study in China reported high response rates with obinutuzumab plus bendamustine, including a 92.9% overall response rate in the WM subgroup. Follow-up was about 13.1 months, so longer-term control is not yet clear from this report. Infections were reported more often in the non-follicular lymphoma group (which included WM), which is a practical reminder that immune suppression can be an important part of the treatment experience. [2]

For patients and caregivers, this month mainly adds reassurance that WM can still respond to more than one type of treatment, including after BTK inhibitor exposure, but it does not identify a single clearly best choice. The bortezomib report reflects a small group treated in one center, and the obinutuzumab-bendamustine study did not compare against another regimen, so these results are better viewed as encouraging options being documented rather than definitive proof. What became clearer is the pattern of side effects reported alongside responses: low blood counts and infections were prominent, while severe neuropathy was not common in the bortezomib series. [1] [2]

This month, studies focused on improving how WM-related proteins and mutations are measured, aiming for more consistent testing and better tracking over time. One large method comparison found strong agreement between two free light chain blood tests, with most disagreements happening near cutoffs that separate normal from abnormal. Another study reported a single test that measures MYD88 and CXCR4 mutations and showed that the mutation level tended to be higher in symptomatic WM and fell in many people responding to ibrutinib. Together, these studies add to the idea that how measurements are made can meaningfully affect how results are interpreted. [3] [4]

In 660 serum samples that included people with WM and related conditions, the Diazyme kappa and lambda free light chain assays on the Roche Cobas platform showed strong analytical performance and 96% clinical concordance with the established Freelite test. The main mismatches were reported near decision thresholds, which matters because small shifts around a cutoff can change how a result is labeled. For patients, this kind of work supports that different laboratories may be able to use different platforms while still producing broadly comparable results. [3]

A separate study developed a multiplex test to measure MYD88 L265P and several CXCR4 mutations and reported that mutation allele frequency (a way to estimate how much tumor DNA is present) was higher in symptomatic WM than in asymptomatic WM or IgM-MGUS. In 37 samples followed during ibrutinib therapy, the mutation signal decreased in people described as responders when measured in tumor DNA, and it also decreased in cell-free DNA, although the report noted that cell-free DNA levels could be very low for monitoring. This points to a potential future role for mutation-level tracking, while also showing that not every sample type may be equally informative. [4]

For patients, these studies are mainly about making testing more reliable and potentially more informative, rather than changing treatment right now. The free light chain validation supports that newer assays can align closely with older ones, but it also clarifies why results may occasionally differ near a cutoff even when nothing major has changed in the body. The mutation-tracking work suggests a future where the amount of MYD88 or CXCR4-mutant DNA could help describe disease activity or response, including during ibrutinib, but the study also highlights limits (for example, not all CXCR4 mutation types were covered and cell-free DNA could be too low to track well). [3] [4]

This month, several single-patient reports highlighted how WM can show up outside the bone marrow or cause organ damage through IgM-related deposits and immune effects. Across these reports, a consistent message was that biopsies and specialized tissue testing helped identify the exact cause, which mattered because different processes can look similar at first. The clinical courses ranged from good organ improvement after therapy to persistent organ failure, underscoring that these are uncommon situations with unpredictable outcomes. [5] [6]

Two kidney-focused reports showed different forms of WM-related kidney injury. One woman had amyloidosis made of both IgM heavy chain and kappa light chain, confirmed by advanced testing of a kidney biopsy, and she later had both a blood (hematologic) response and a kidney response after bendamustine plus rituximab with 43 months of follow-up. Another patient had IgM-kappa deposition disease with very aggressive crescentic glomerulonephritis plus thrombotic microangiopathy on kidney biopsy and remained dialysis-dependent despite clone-directed therapy. [5] [6]

One report described a patient on ibrutinib who developed cerebral aspergillosis after an influenza infection, along with probable invasive pulmonary aspergillosis, and the brain infection was controlled with surgery and isavuconazole. This case adds to awareness that serious fungal infections can occur in this setting and that tissue-based molecular testing can help confirm the cause. Because it is one patient, it cannot show how often this happens, but it documents a specific clinical pattern and how it was managed. [7]

Two additional reports described rarer diagnostic and disease-overlap situations. One patient had focal liver lesions where biopsy showed granulomatous inflammation with IgM-positive, lambda-restricted B cells linked to the WM clone, and the liver findings improved after bendamustine-rituximab even though low blood counts and infections were part of the course. Another patient initially treated for WM was later understood to have smoldering WM with coexisting myelodysplastic syndrome, where persistent low blood counts signaled a second bone marrow problem and the course progressed to acute myeloid leukemia driven by a new FLT3-ITD mutation. [8] [9]

For patients and caregivers, these reports mainly add recognition of the range of complications that can occur, rather than providing general predictions. The shared practical point is that when symptoms involve an organ like the kidney, liver, or brain, tissue testing in these cases helped identify the exact process (amyloid, immunoglobulin deposits, granulomatous inflammation, or infection), and that clarity shaped the next steps taken in each report. What remains uncertain is how often any of these situations occur and which people are at highest risk, because case reports cannot answer those questions. This information may matter most when someone faces an unexpected complication or an unusual scan or lab result and needs a clear explanation of what it could represent. [5] [6] [7] [8] [9]

This month included a large real-world analysis suggesting that where someone starts socially and economically can be tied to WM outcomes. In SEER data covering 8256 people diagnosed from 2006 to 2020, lower socioeconomic status was linked to worse overall survival and to higher chemotherapy use. Differences in cancer-specific survival were not obvious in simpler analyses but appeared after more adjustment, and the patterns varied across racial and ethnic groups. [10]

The study reported that low socioeconomic status was associated with increased all-cause mortality (HR 1.37) and greater chemotherapy use (OR 1.33). When the researchers looked within racial and ethnic groups, low socioeconomic status tracked with worse overall survival in non-Hispanic White and Hispanic patients, but not in non-Hispanic Black patients in that stratified analysis. For patients, this frames survival differences as not only about biology, but also about broader factors that can shape access, timing, and the type of care people receive. [10]

For patients, this study mainly adds context about why outcomes can differ between groups, and it helps validate that social and financial conditions can show up in survival statistics. It does not explain which specific factors (such as delays in diagnosis, access to specialists, or differences in supportive care) drove the differences, because registry data do not capture those details. This may matter now as background for understanding population-level disparities, and it may matter later if future studies identify which barriers are most changeable. [10]