{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:08:42Z","timestamp":1792796922649,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100001422","name":"American Society of Hematology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001422","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Venetoclax and pirtobrutinib have emerged as two chemotherapy\u2010free options for relapsed or refractory Waldenstr\u00f6m macroglobulinemia (WM). However, evidence to guide treatment sequencing or identify molecular subsets most likely to benefit from each agent remains limited. We retrospectively evaluated consecutive WM patients treated with venetoclax or pirtobrutinib. Major response rate (MRR) and progression\u2010free survival (PFS) were assessed for each agent, with predictors of response and PFS analyzed using logistic and Cox regression. Comparative efficacy was examined in unmatched analyses and in a 1:1 matched cohort. Among 91 treatment exposures (64 venetoclax and 27 pirtobrutinib) across 80 unique patients, treatment discontinuation due to adverse effects occurred in 12 of 64 patients (19%) treated with venetoclax and in none treated with pirtobrutinib. In the venetoclax cohort,\n                    <jats:italic>TP53<\/jats:italic>\n                    alterations were associated with shorter PFS (10.0 vs. 35.6\u2009months;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). In the pirtobrutinib cohort,\n                    <jats:italic>CXCR4<\/jats:italic>\n                    mutations predicted lower MRR (40% vs. 91%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01) and shorter PFS (8.3\u2009months vs. not reached;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02). When transitioning from a cBTKi, IgM rebound occurred in 62% (8\/13) of patients initiating venetoclax without overlap, whereas no rebound was observed with cBTKi\u2010venetoclax overlap (0\/5) or with pirtobrutinib initiation (0\/15). In the matched cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200942), venetoclax and pirtobrutinib demonstrated comparable outcomes for MRR (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.91) and PFS (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.83). Despite the retrospective design and limited sample size, these findings indicate comparable efficacy between venetoclax and pirtobrutinib with distinct molecular vulnerabilities and support consideration of pirtobrutinib sequencing when transitioning from a cBTKi, as well as further exploration of combination strategies that may exploit complementary vulnerabilities.\n                  <\/jats:p>","DOI":"10.1002\/ajh.70269","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:42:36Z","timestamp":1772988156000},"page":"1045-1055","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Venetoclax or Pirtobrutinib in Relapsed\/Refractory Waldenstr\u00f6m Macroglobulinemia: Clinical and Molecular Predictors and Sequencing Implications"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8205-6643","authenticated-orcid":false,"given":"Alberto","family":"Guijosa","sequence":"first","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nickolas","family":"Tsakamaklis","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Kobs","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Kofides","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Budano","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Eurell","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Meid","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Guerrera","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1689-1691","authenticated-orcid":false,"given":"Zachary R.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6393-6154","authenticated-orcid":false,"given":"Steven P.","family":"Treon","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayna","family":"Sarosiek","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber Cancer Institute  Boston Massachusetts USA"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge J.","family":"Castillo","sequence":"additional","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana\u2010Farber 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