Lymphoplasmacytic Lymphoma

Our NGS testing found tier 1 or 2 variants in the majority of cases, supporting its use in the clinical setting. Additionally, a subset of variants identified with the pan-Heme list likely represents mutations of clonal hematopoiesis of indeterminate potential, which could be removed with a more lymphoma-specific gene list. Given these findings, and a growing number of targets in indolent B cell lymphomas, future studies focusing on evaluation of a lymphoma-specific gene list is of interest for clinical validation and implementation.

P2, N=17, Completed, University College, London | Trial completion date: Jun 2023 --> Feb 2024

We present the 6-year update of a phase 2 study evaluating the combination of obinutuzumab and idelalisib in relapse/refractory Waldenstrom macroglobulinemia. Moreover, ibrutinib remains an effective treatment after this combination. This study was registered on the clinicaltrial.gov web (NCT02962401, November 9, 2016).

P=N/A, N=200, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

With a median follow-up of 73 months, the median TTNT in patients with and without CAs was 27 and 68 months, respectively. CAs with CBA may be associated with clinical aggressiveness and shorter TTNT in sWM.

P2, N=46, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2024 --> Jun 2026

P1, N=42, Not yet recruiting, Washington University School of Medicine

Testing for MYD88 mutations using AS-PCR or ddPCR in unsorted samples is viable for routine clinical practice. Under BTKi treatment, MYD88 and CXCR4 mutations hold greater prognostic importance than IPSSWM staging in WM.

P=N/A, N=605, Recruiting, iOMEDICO AG | N=400 --> 605 | Trial completion date: Apr 2027 --> Aug 2028 | Trial primary completion date: Apr 2027 --> Aug 2028

No abstract available

P=N/A, N=40, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Jan 2025 --> May 2025 | Trial primary completion date: Jul 2024 --> Jan 2025

Based on radiographic findings, a diagnosis of paraneoplastic LETM was made and he was treated acutely with IV methylprednisolone followed by a quick oral prednisone taper. However, he subsequently relapsed and symptomatically worsened while on rituximab therapy...Our observation of sustained disease response in this patient may support a role for concurrent BTK and BCL2 inhibition in paraneoplastic myelitis associated with B-cell lymphoproliferative disorders. However, this observation needs to be validated in larger cohort studies and potentially in clinical trials if further data are supportive.

P1, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

We show that pirtobrutinib blocked p-ERK1/2, ERK1/2-driven inflammatory cytokines, and overcame paracrine-mediated resistance in MYD88Mut lymphoma cells expressing mutated BTKCys481. Our results provide important mechanistic insights for the activity of pirtobrutinib in MYD88Mut lymphomas carrying BTKCys481 mutations.

P2, N=22, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Jun 2024 --> Jun 2025

P1, N=8, Active, not recruiting, Joseph Tuscano | Trial completion date: Dec 2024 --> Jul 2025 | Trial primary completion date: Apr 2024 --> Dec 2024

P2, N=120, Active, not recruiting, Cellectar Biosciences, Inc. | Trial completion date: Jun 2025 --> Dec 2026 | Recruiting --> Active, not recruiting

P2, N=17, Active, not recruiting, University of Maryland, Baltimore | N=34 --> 17

The discovery of the recurrent MYD88L265P gain-of-function point mutation and the subclonal CXCR4 mutations has helped improve our understanding of the WM biology, and the prognostic impact of these mutations is under evaluation, with somewhat inconsistent findings thus far across studies. This review discusses the clinical presentation, diagnostic criteria, and prognostic markers of WM.

These clinical cases emphasize the challenges in diagnosing BNS. Based on the findings, biopsy is recommended for accurate identification of the clonal relationship and MYD88 mutation status.

In conclusion, composite lymphoma can present in the bone marrow. The use of ancillary studies was essential in reaching the diagnosis in this case, as the results excluded the possibility of MCL lymphoma with plasmacytic differentiation, as well as other CD5- and CD10-negative small B-cell lymphomas.

P2, N=42, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | N=30 --> 42

P1, N=16, Completed, X4 Pharmaceuticals | Phase classification: P1b --> P1

P3, N=1272, Active, not recruiting, Jurgen Barth | Trial completion date: Apr 2030 --> Dec 2024 | Trial primary completion date: Apr 2030 --> Dec 2024

Treatment was well tolerated, with minimal numbers of immune-mediated AEs typically seen with checkpoint inhibitors. PembroWM is the first study to evaluate the feasibility of PD-1 axis modulation in WM and has shown that in combination with Rituximab the combination is safe and deliverable.

P2, N=55, Not yet recruiting, Massachusetts General Hospital

P1, N=18, Completed, Calibr, a division of Scripps Research | Active, not recruiting --> Completed

P1, N=46, Completed, Ascentage Pharma Group Inc. | Recruiting --> Completed | N=123 --> 46 | Trial completion date: Dec 2025 --> Feb 2024 | Trial primary completion date: Dec 2024 --> Feb 2024

No abstract available

Vaccine therapy activates and expands bone marrow T-cell clonotypes, and functional neoantigen-specific responses (secondary endpoint), but not co-inhibitory pathways or Treg, and reduces protumoral signaling by myeloid cells, suggesting favorable perturbation of the tumor immune microenvironment. Future strategies may require combinations of vaccines with agents targeting plasma cell subpopulations, or blockade of IGF-1 signaling or myeloid cell checkpoints.

P2, N=102, Not yet recruiting, French Innovative Leukemia Organisation

Caution is advised when using a homogenous method for direct measurement of HDL-C and LDL-C in patients with monoclonal paraprotein. Techniques to recognize and eliminate this interference are available. However, immunoturbidimetric detection of apoA-I and apoB levels is also susceptible to this interference, which is not readily removable.

P1, N=27, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024

BTK signaling is implicated in various B-cell lymphomas such as mantle cell lymphoma, Waldenström Macroglobulinemia, follicular lymphoma, and diffuse large B cell lymphoma, leading to the development of transformative treatments like ibrutinib, the first-in-class covalent BTK inhibitor, and pirtobrutinib, the first-in-class noncovalent BTK inhibitor. This non-enzymatic role promotes cell survival and proliferation independently of kinase activity. Understanding BTK's dual roles unveils opportunities for therapeutics targeting its scaffolding function, promising advancements in disrupting lymphomagenesis and refining B cell lymphoma treatments.

P=N/A, N=10000, Recruiting, Dana-Farber Cancer Institute | N=1000 --> 10000 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=19, Active, not recruiting, Kite, A Gilead Company | Recruiting --> Active, not recruiting | N=90 --> 19

Clinically meaningful differences were observed in diarrhea and nausea/vomiting in both the intent-to-treat population and in patients attaining very good partial response (VGPR) in earlier cycles of treatment, as well as in long-term physical functioning and fatigue in patients achieving VGPR. Treatment with zanubrutinib was associated with greater improvements in health-related quality of life compared with ibrutinib in patients with WM and MYD88 mutations.Clinical Trial Registration: NCT03053440 (ClinicalTrials.gov).

This synergistic activity was also observed in Waldenström's Macroglobulinemia (WM) cells and with other inhibitors of E2F1 activity. Dual inhibition effectively impaired the MYC and E2F transcriptional programs and MM tumor growth and progression in xenograft animal models, providing evidence for combination therapy's potential as a therapeutic strategy in MM and WM.

P1, N=266, Recruiting, Nurix Therapeutics, Inc. | Active, not recruiting --> Recruiting | N=160 --> 266 | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

Affected members of each pedigree shared multiple deleterious variants (median, n = 18), but the overlap between the families was modest. In summary, P/LP variants in highly penetrant genes constitute a modest proportion of the deleterious variants; each pedigree is largely unique in its genetic architecture, and multiple genes are likely involved in the etiology of WM.

P1/2, N=20, Terminated, Mustang Bio | N=287 --> 20 | Trial completion date: Sep 2026 --> Apr 2024 | Recruiting --> Terminated | Trial primary completion date: Sep 2026 --> Apr 2024; Business reasons

P=N/A, N=3, Terminated, Mustang Bio | N=331 --> 3 | Trial completion date: Jul 2041 --> Apr 2024 | Enrolling by invitation --> Terminated | Trial primary completion date: Apr 2041 --> Apr 2024; Business Reasons