International Phase III Study of Chlorambucil Versus Fludarabine As Initial Therapy for Waldenstrom's Macroglobulinemia and Related Disorders: Results in 414 Patients on Behalf of FCG CLL/ WM, GOELAMS, GELA, NCRI, ALLG

Abstract Abstract 776 Background: Waldenstrom's macroglobulinemia (WM) and related-disorders (Marginal Zone Lymphoma: MZL, and non immunoglobulin IgM lymphoplasmacytic lymphoma: LPL) are rare diseases Very few randomized trials were reported in this setting. Most commonly patients with WM are initially treated with an alkylating agent, such as chlorambucil (CBL) or with a nucleoside analogue such as fludarabine (F) or 2CdA, alone or in association with monoclonal antibody. Methods: WM1 study was a prospective international randomized open-label study that included patients with previously untreated WM MZL and LPL. At registration, patients were stratified as having WM, SLVL, or LPL, and were randomized in the two arms. The aim of the study was to compare the efficacy of oral CBL at a dose of 8 mg/m2 for 10 days every 28 days to a maximum of 12 cycles with oral F at a dose of 40 mg/m2 orally for 5 days every 28 days to a maximum of 6 cycles. 418 patients were enrolled into the study from 07/01 to12/09. 414 patients were included and 405 received at least one course of chemotherapy. There were 339 WM, 37 MZL and 38 LPL with a median age of 68 years (40-89). 207 patients were randomized in the F arm and 207 patients in the CBL arm. At inclusion, the median of haemoglobin (g/l), platelets (Giga/l), albumin (g/l) and beta 2 microglobulin (mg/l) were 9.9, 218, 37.1 and 3.47 respectively. Results: In intention to treat basis, the overall response rate (CR+PR) was 47.8 % in the F arm versus 38.6% in the CBL arm (p=0.06). With a median follow-up time of 35.9 months, the median of progression free survival time (PFS) and disease free survival (DFS) were statistically longer in the F arm: PFS 36.3m vs 27.1 m ( p=0.01) and DFS 38.3m vs 19. 9m (p= 0.0006). In WM group, factors influencing negatively PFS were CBL arm, albumin< 35g/l, platelets<100 G/l and age> 70 years. Main toxicity was haematological with 17/203 (8.3%) vs 18/203 (9%) of grade III- IV thrombocytopenia and 50/203 (24.6%) vs 39/202 (19.3%) of grade III-IV anemia in F and CBL arms respectively. Overall survival rate at 5 years was 61.4% [52.9;71.3] in CBL arm and 70.3% [62.7-78.8] in F arm (p=0.04) (Fig 1). Cumulative Incidence of second malignancies (solid tumors and haematological malignancies except Richter syndrome (RS)) was statistically higher in the chlorambucil arm (25 versus 8, p= 0.004) (Fig 2). The number of RS was 8 in F arm and 9 in CBL arm. Conclusion: F by oral route is a safe and effective ambulatory treatment in WM and close related disorders patients, even in the elderly and more effective than CBL with a duration of response over 3 years. An unexpected finding was a statistically higher number of second malignancies in the C arm and we cannot rule out an oncogenic role of CBL in this setting. Of note, we stress that it is the first time that a front- line treatment has a significant impact on overall survival in WM patients. Disclosures: Leblond: mundipharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tournilhac:Amgen: Research Funding; Mundipharma: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees.

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Phase II Trial of Weekly Bortezomib in Combination with Rituximab in Relapsed or Relapsed/Refractory Waldenstrom's Macroglobulinemia.

Blood ◽

10.1182/blood.v114.22.2727.2727 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2727-2727

Author(s):

Irene M. Ghobrial ◽

Fangxin Hong ◽

Swaminathan Padmanabhan ◽

Ashraf Z. Badros ◽

Meghan Rourke ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Significant Activity ◽

Waldenström’S Macroglobulinemia ◽

Advisory Committees ◽

Minor Response ◽

Waldenstrom's Macroglobulinemia ◽

Waldenstrom’S Macroglobulinemia ◽

Grade 3 ◽

Waldenström's Macroglobulinemia

Abstract Abstract 2727 Poster Board II-703 INTRODUCTION: This study aimed to determine activity and safety of weekly bortezomib and rituximab in patients with relapsed/refractory Waldenstrom's Macroglobulinemia (WM). METHODS: Patients who had at least one previous therapy were eligible. All patients received bortezomib IV weekly at 1.6 mg/m2 on days 1, 8, 15, q 28 days x 6 cycles, and rituximab 375 mg/m2 weekly on cycles 1 and 4. Primary endpoint was the percent of patients with at least a minor response. RESULTS: Thirty-seven patients were treated. Majority of patients (78%) completed treatment per protocol. At least minimal response (MR) or better was observed in 81% (95% CI: [65,92]) with 2 patients (5%) in complete remission (CR)/near CR, 17 (46%) in partial response (PR), and 11(30%) in MR. The median time to progression was 16.4 months (95% CI, 11.4–21.1). Death occurred in 1 patient due to viral pneumonia. The most common grade 3 and 4 therapy related adverse events included reversible neutropenia in 16%, anemia in 11%, and thrombocytopenia in 14%. Grade-3 peripheral neuropathy occurred in only 2 patients (5%). The median event-free survival (EFS) is 12 months (95% CI, 11–20) with estimated 12 month and 18 month EFS of 49% (95% CI: [31, 67%]) and 38% (95% CI: [20, 56%]). The median overall survival has not been reached. CONCLUSIONS: The combination of weekly bortezomib and rituximab showed significant activity and minimal neurological toxicity in patients with relapsed WM. Disclosures: Ghobrial: Millennium: Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Anderson:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Millennium: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Richardson:Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keryx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Treon:Millennium: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Genentech: Honoraria, Research Funding, Speakers Bureau. Matous:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cephalon: Membership on an entity's Board of Directors or advisory committees.

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Combining Ixazomib With Subcutaneous Rituximab and Dexamethasone in Relapsed or Refractory Waldenström's Macroglobulinemia: Final Analysis of the Phase I/II HOVON124/ECWM-R2 Study

Journal of Clinical Oncology ◽

10.1200/jco.21.00105 ◽

2021 ◽

pp. JCO.21.00105

Author(s):

Marie José Kersten ◽

Karima Amaador ◽

Monique C. Minnema ◽

Josephine M. I. Vos ◽

Kazem Nasserinejad ◽

...

Keyword(s):

Overall Survival ◽

Phase I ◽

Progression Free Survival ◽

Immunoglobulin M ◽

Waldenström’S Macroglobulinemia ◽

Minor Response ◽

Free Survival ◽

Waldenstrom's Macroglobulinemia ◽

Waldenstrom’S Macroglobulinemia ◽

Waldenström's Macroglobulinemia

PURPOSE Proteasome inhibitors are effective in Waldenström's macroglobulinemia (WM) but require parenteral administration and are associated with polyneuropathy. We investigated efficacy and toxicity of the less neurotoxic oral proteasome inhibitor ixazomib combined with rituximab, in patients with relapsed WM. METHODS We conducted a multicenter phase I/II trial with ixazomib, rituximab, and dexamethasone (IRD). Induction consisted of eight cycles IRD wherein rituximab was started in cycle 3, followed by rituximab maintenance. Phase I showed feasibility of 4 mg ixazomib. Primary end point for phase II was overall response rate (ORR [≥ minimal response]) after induction. RESULTS A total of 59 patients were enrolled (median age, 69 years; range, 46-91 years). Median number of prior treatments was 2 (range 1-7); 70% had an intermediate or high WM-IPSS (International Prognostic Scoring System for WM) score. After eight cycles, ORR was 71% (42 out of 59) (14% very good partial response [PR], 37% PR, and 20% minor response). Depth of response improved until month 12 (best ORR 85% [50 out of 59]: 15% very good PR, 46% PR, and 24% minor response). Median duration of response was 36 months. The average hematocrit level increased significantly (0.33-0.38 L/L) after induction ( P < .001). After two cycles of ixazomib and dexamethasone, immunoglobulin M levels decreased significantly (median 3,700-2,700 mg/dL, P < .0001). Median time to first response was 4 months. Median progression-free survival and overall survival were not reached. After median follow-up of 24 months (range, 7.4-54.3 months), progression-free survival and overall survival were 56% and 88%, respectively. Toxicity included mostly grade 2 or 3 cytopenias, grade 1 or 2 neurotoxicity, and grade 2 or 3 infections. No infusion-related reactions or immunoglobulin M flare occurred with use of subcutaneous rituximab. Quality of life improved significantly after induction. In total, 48 patients (81%) completed at least six cycles of IRD. CONCLUSION Combination of IRD shows promising efficacy with manageable toxicity in patients with relapsed or refractory WM.

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A Phase II Trial of the Oral mTOR Inhibitor Everolimus (RAD001) in Relapsed or Refractory Waldenstrom's Macroglobulinemia.

Blood ◽

10.1182/blood.v114.22.587.587 ◽

2009 ◽

Vol 114 (22) ◽

pp. 587-587

Author(s):

Irene M Ghobrial ◽

Morie A Gertz ◽

Betsy LaPlant ◽

John Camoriano ◽

Suzanne R. Hayman ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Overall Response Rate ◽

Response Rate ◽

Single Agent ◽

Waldenström’S Macroglobulinemia ◽

Advisory Committees ◽

Overall Response ◽

Waldenstrom's Macroglobulinemia ◽

Waldenström's Macroglobulinemia

Abstract Abstract 587 Background: The phosphatidylinositol 3-kinase/mammalian target of rapamycin (mTOR) signal transduction pathway controls cell proliferation and survival. Everolimus is an oral agent targeting raptor mTOR (mTORC1). The trial's goal was to determine the anti-tumor activity and safety of single-agent everolimus in patients with relapsed/refractory Waldenstrom's macroglobulinemia (WM). Patients and Methods: Eligible patients had measurable disease (IgM monoclonal protein >1000 mg/dL with >10% marrow involvement or nodal masses >2 cm), a platelet count ≥75,000 × 106/L, a neutrophil count ≥1,000 × 106/L, and a creatinine and bilirubin ≤2x laboratory upper limit of normal. Patients received everolimus 10 mg PO daily and were evaluated monthly. Tumor response was assessed after cycles 2 and 6 and then every 3 cycles until progression. Results: 50 pts were treated. The median age was 63 years (range, 43-85). The overall response rate (CR+PR+MR) was 70% (95% CI: 55-82%), with a PR of 42% and 28% MR. The median duration of response and median progression-free survival (PFS) has not been reached. The estimated PFS at 6 and 12 months is 75% (95%CI: 64-89%) and 62% (95%CI: 48-80%), respectively. Grade 3 or higher related toxicities were observed in 56% of patients. The most common were hematological toxicities with cytopenias. Pulmonary toxicity occurred in 10% of patients. Dose reductions due to toxicity occurred in 52% of patients. Conclusions: Everolimus has high single-agent activity with an overall response rate of 70% and manageable toxicity in patients with relapsed WM, and offers a potential new therapeutic strategy for this patient group. Disclosures: Ghobrial: Millennium: Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Gertz:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Richardson:Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keryx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Treon:Millennium: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Genentech: Honoraria, Research Funding, Speakers Bureau. Witzig:Novartis: Research Funding.

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Long-lasting responses after four doses of rituximab in Waldenström's macroglobulinemia: Clinical value of minor responses: A follow-up of the Eastern Cooperative Oncology Group E3A98 trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8513 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8513-8513

Author(s):

M. A. Gertz ◽

R. Abonour ◽

L. T. Heffner ◽

P. R. Greipp ◽

H. Uno ◽

...

Keyword(s):

Objective Response ◽

Progression Free Survival ◽

Waldenström’S Macroglobulinemia ◽

Minor Response ◽

Free Survival ◽

Previously Treated ◽

Waldenstrom's Macroglobulinemia ◽

Waldenstrom’S Macroglobulinemia ◽

A Minor ◽

Waldenström's Macroglobulinemia

8513 Background: Waldenström's macroglobulinemia is a low-grade lymphoplasmacytic lymphoma that is responsive to rituximab. Uniform response criteria define an objective response as a 50% reduction in the IgM level, and a minor response as a 25% reduction in IgM level. No publications in the literature exist that justify the use of the minor response. Clinicians who treat patients that achieve a minor response are left uncertain as to whether the response is adequate and patients should be monitored for progression or whether they should be considered therapy failures and crossover to an alternate chemotherapy regimen in an effort to achieve a deeper response. Methods: 69 patients, 34 previously untreated, and 35 previously treated (but rituximab naive) were included. All patients were treated with a single four-week course of rituximab 375 mg/m2 and were monitored with no further therapy until progression. Results: There were 19 objective and 17 minor responses out of 69 eligible patients (52.2%). Response rate and progression-free survival (26.6 mo) were similar whether patients were previously untreated or previously treated. Previously treated rituximab-naïve and previously untreated patients had, five-year survivals of 48% and 85%, respectively. There was no difference in overall or progression free survival between patients who achieved an objective response when compared to those who achieved a minor response. There was no difference between objective and minor responders by age, time from diagnosis to treatment in the treated group, bone marrow lymphoplasmacytes, hemoglobin level, creatinine, IgM level, or M-spike. The pre-treatment level of IgM did not predict overall survival, progression-free survival, time to progression, or response rate (All p>0.05). This lack of significance was found whether IgM was assessed as a continuous or discrete variable. Conclusions: These results reconfirm rituximab's efficacy as a single-agent for the treatment of Waldenström's macroglobulinemia, and patients who have a 25–50% reduction in their IgM protein derive significant clinical benefits that are durable and appear to not have an impact on overall survival. No significant financial relationships to disclose.

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Waldenstrom's Macroglobulinemia: A SEER Database Review From 1981-2005.

Blood ◽

10.1182/blood.v114.22.2926.2926 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2926-2926

Author(s):

Jeevan Sekhar ◽

Daniel Morgensztern ◽

Qin Zhang ◽

Ravi Vij

Keyword(s):

Overall Survival ◽

Seer Database ◽

Waldenström’S Macroglobulinemia ◽

Quarter Century ◽

Small Series ◽

Time Period ◽

Significant Difference ◽

Waldenstrom's Macroglobulinemia ◽

Waldenstrom’S Macroglobulinemia ◽

Waldenström's Macroglobulinemia

Abstract Abstract 2926 Poster Board II-902 Introduction: Waldenstrom's Macroglobulinemia (WM) is a relatively rare hematopoietic neoplasm, with literature data mostly limited to small series of patients. We conducted a review of the Surveillance Epidemiology and End Results (SEER) database for WM analyzing 2969 cases from 1981-2005. Results: The incidence of reported cases of WM was stable during the studied time period at 0.3 per 100,000. The median age at diagnosis was 73 (range 23-98). There were 1661 male cases of WM and 1038 female cases (incidence ratio of 1.6:1). There were 2435 Caucasian cases and 264 non-Caucasian cases (incidence ratio of 9.2:1). Median overall survival for the entire cohort was 65 months (95% CI, 61-69). Five-year overall survival was 52% (95% CI, 50-55%). There was a significant difference in survival for individuals age <60 years versus age ≥60 years with age-adjusted 5 year overall survivals of 78% (95% CI, 44-49%) and 47% (95% CI, 44-49%), p<0.0001, respectively. Gender and race had no impact on overall survival (p=0.23 and 0.13, respectively). There was no improvement in survival over the time period analyzed. The cohort of patients diagnosed in 1981-1995 had a 5-year overall survival of 50% (95% CI, 46-54%), and those diagnosed in 1996-2005 had a 5-year overall survival of 54% (95%CI, 51-57%), p=0.18. Conclusion: This survey represents the largest cohort of WM analyzed to date. Age was shown to be the sole predictor of overall survival. Furthermore, these results underscore the little therapeutic progress we have made for this disease considering the lack of improvement in overall survival over a quarter century. Disclosures: Vij: Otsuka Pharmaceuticals: Research Funding.

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Incidence of Transformation to Large Cell Lymphoma and to Second Malignancies in Symptomatic Patients with Waldenstrom’s Macroglobulinemia (WM) Treated with Cladribine (2-CdA) Combination Induction Therapy

Blood ◽

10.1182/blood.v112.11.3065.3065 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3065-3065 ◽

Cited By ~ 2

Author(s):

Ronjay Rakkhit ◽

Kay B Delasalle ◽

Maria B. Gavino ◽

Sheeba K. Thomas ◽

Meletios A Dimopoulos ◽

...

Keyword(s):

Cell Lymphoma ◽

Large Cell ◽

Nucleoside Analogues ◽

Second Malignancy ◽

Second Malignancies ◽

Waldenström’S Macroglobulinemia ◽

Waldenstrom's Macroglobulinemia ◽

Large Cell Lymphoma ◽

Waldenstrom’S Macroglobulinemia ◽

Waldenström's Macroglobulinemia

Abstract Waldenstrom’s macroglobulinemia (WM) is an incurable malignancy characterized by malignant proliferation of lymphoplasmacytoid cells that produce a monoclonal IgM. Treatment of this disorder with nucleoside analogues like 2-CdA and fludarabine have resulted in excellent response rates and subsequent median survivals of approximately 8–9 years for previously untreated patients at our center. We, and others, have previously questioned the impact of initial treatment of Waldenstrom’s Macroglobulinemia on the risk of development of second malignancy and transformation (TR) to aggressive NHL (Non-Hodgkin’s Lymphoma). The objective of this analysis was to determine the incidence of transformation to large cell lymphoma and second malignancies in patients (pts) treated with 2-CdA either alone or in combination for induction therapy of patients with symptomatic WM. We performed a retrospective analysis of 111 consecutive, previously untreated patients with symptomatic WM who were treated with using 2 consecutive 4–6-week courses of either 2-CdA alone or in combination with other agents including prednisone (pred), cyclophosphamide (Cy), and rituximab (Rit) between January 1991 – July 2005. Patients received either 2-CdA 0.1 mg/kg by continuous infusion (CI) over 24 hours (hrs) × 7 days (n=16), an identical program with prednisone 60 mg/m2/d po for 7 days (n=22), 2-CdA 1.5 mg/m2 by subcutaneous injection (SC) q8 hrs × 7d + Cy 40 mg/m2 p.o. b.i.d. × 7d (n= 38), or identical 2-CdA (SC) + Cy + Rit 375 mg/m2 by intravenous infusion (IV) weekly × 4 weeks (n=35). Among 111 pts, 23 (21%) had either transformation to large cell lymphoma or development of a second malignancy within a median of 55 months. Ten patients (9%) had transformation to large cell lymphoma after treatment with 2-CdA alone (3 pts), 2-CdA/pred (1 pts), 2-CdA/Cy (3 pts) and 2CdA/Cy/Rit(3 pts). The median time to development of transformation to large cell lymphoma was 37 months (1mo – 110 mo) and 4 pts had transformation of disease within 13 months. An additional 13 pts (12%) developed other second malignancies including breast cancer (ca) (2pts), renal cell ca (2 pts), Basal cell ca of skin (2 pts), Hodgkin’s lymphomas (2 pts), cervical ca (1 pt), ovarian ca (1 pt), colorectal ca (1 pt), mesothelioma (1 pt), head/neck squamous cell ca (1 pt), vascular sarcoma (1 pt), bladder ca (1 pt) and prostate ca (1 pt), AML (1 pt) after treatment with 2-CdA (5 pts), 2-CdA/pred (1 pt), 2-CdA/Cy (4 pts), and 2CdA/Cy/Rit (3 pts). The median time to development of a second malignancy was 85.5 months and there did not appear to be any significant trend towards development of any particular secondary malignancy. While 2-CdA based induction regimens for WM provide excellent cause-specific survival for WM, this analysis suggests that the incidence of large cell transformation and second malignancies is pronounced among this group of patients with Waldenstrom’s Macroglobulinemia. Whether this rate of transformation/second malignancy is related to treatment with nucleoside analogues, or due to the natural progression of disease in patients with long survival after treatment with 2-CdA regimens remains unclear. We are currently extending the retrospective analysis to include a similar historic cohort of patients treated with alkylating agents and will provide updated data regarding both groups of patients at the time of presentation.

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Global Waldenström's Macroglobulinemia Patient-Derived Data Registry, Whimsical, Highlights Real-World Treatment Outcomes and COVID-19 Data

Blood ◽

10.1182/blood-2021-147720 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1343-1343

Author(s):

Ibrahim Tohidi-Esfahani ◽

Andrew Warden ◽

Elena Malunis ◽

Peter Liburdi deNardis ◽

Michelle Postek ◽

...

Keyword(s):

Real World ◽

Research Funding ◽

Waldenström’S Macroglobulinemia ◽

First Line ◽

Advisory Committees ◽

Eortc Qlq C30 ◽

Waldenstrom's Macroglobulinemia ◽

Waldenstrom’S Macroglobulinemia ◽

Eortc Qlq ◽

Waldenström's Macroglobulinemia

Abstract Introduction: WhiMSICAL (Waldenström's Macroglobulinemia Study Involving CArt-wheeL) is the first global Waldenström's Macroglobulinemia (WM) registry capturing patient-derived data to complement scarce clinical trials data in this rare cancer (Tohidi-Esfahani et al, Am J Hematol 2021). The registry was interrogated to identify real-world first line treatment outcomes, quality of life (QoL) and coronavirus disease 2019 (COVID-19) data. Methods: The registry captures data through www.cart-wheel.org, an online rare cancer database, utilizing a tailored questionnaire developed by clinician and patient investigators. WM patients complete consent online, then enter symptom, pathology, treatment, QoL (EORTC QLQ-C30) and COVID-19 data, and can return to update their data on an ongoing basis. Recruitment is driven by social media messaging by the International Waldenström's Macroglobulinemia Foundation investigators. Time to next treatment (TTNT) was assessed from start of first therapy to start of second therapy. Patients without a documented second therapy were censored at the time of last edit to their account. COVID-19 questions included testing, disease severity, vaccination and impact on WM management. Results: As of July 2021, 558 patients from 20 countries have participated in the registry, predominantly from USA (50%), Australia (22%) and the UK (9%). Median age at diagnosis was 61 years (range 24-83) with male predominance (61%). 371 patients documented first-line therapies, with a total of 54 unique therapeutic combinations listed. The seven most common therapies were: bendamustine rituximab (BR, n=94), rituximab monotherapy (Rit., n=52), dexamethasone rituximab cyclophosphamide (DRC, n=33), ibrutinib (n=25), bortezomib dexamethasone rituximab (n=15), rituximab cyclophosphamide vincristine prednisolone (n=14) and chlorambucil (n=10). Comparison of TTNT was limited to the four most common first-line therapies: BR, Rit., DRC, with zanubrutinib (n=5) and ibrutinib plus rituximab (n=2) adding to the first line Bruton tyrosine Kinase inhibitor (BTKi) cohort (n=32). Median ages for the BR, BTKi, DRC and Rit. cohorts were 65, 66, 61 & 65 years, respectively. More patients in the BR cohort listed comorbidities (37%), with BTKi-treated patients reporting the least (19%). Pre-treatment disease burden (median IgM and hemoglobin) trended to being higher in the BR and DRC cohorts (figure 1B-D, IgM p=0.24, Hb p=0.27). At median follow up ranging from 31 to 39 months, BR had superior TTNT to DRC (median: not reached and 104 months, p=0.007, figure 1C) and Rit. (median 26 months, p < 0.0001, figure 1D), and trended to superiority compared to BTKi (median not reached, p=0.08, figure 1B). Median TTNT for the entire cohort (n=371) was 108 months (median follow up 55 months, figure 1A). Assessment of QoL was conducted in all patients (any line of treatment) and compared between patients currently on BTKi therapy (n=64) and patients not exposed to BTKi and treated within the last 12 months (n=84). The expanded BTKi cohort reported better QoL, with mean EORTC QLQ-C30 global scale of 82 ± 14.4 compared to the BTKi-naïve cohort mean 73.4 ± 20.9, p=0.005. This was despite more prior lines of treatment (median 2 [IQR 1-4] compared to 1 [IQR 1-1]; p<0.0001). 324 (58%) patients responded to the COVID-19 questions. 144/324 (44%) had undergone testing for COVID-19, with 11 (8%) returning a positive result; none after vaccination. Median length of symptoms was seven days (range 2-30), with two hospitalized, one requiring intensive care. Both hospitalized patients were on second line ibrutinib. Of 211 responses regarding vaccination status, 15 (7%) were not vaccinated, eight due to availability, five due to personal choice and two due to clinician advice. Regarding impact of the pandemic on their WM management, 5% had treatment schedule disruption and 53% reported reduced face-to-face consultations. Conclusion: The WhiMSICAL registry provides a scientifically robust and ethically approved portal for the patients' voice. The data highlight the real-world efficacy of combination chemoimmunotherapy, particularly first-line BR, and suggest a better QoL with BTKi than other therapies. As this global data platform grows, the breadth of data allows for new insights into WM with patient reported outcomes advancing knowledge and facilitating treatment decisions for clinicians and patients. Figure 1 Figure 1. Disclosures D'Sa: Sanofi: Honoraria; BeiGene: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding. Kersten: Roche: Consultancy, Honoraria, Other: Travel support, Research Funding; Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support; Novartis: Consultancy, Honoraria, Other: Travel support; BMS/Celgene: Consultancy, Honoraria; Takeda: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding; Celgene: Research Funding. Thomas: Acerta Pharma: Research Funding; Ascentage Pharma: Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; X4 Pharma: Research Funding; Genentech: Research Funding. Palomba: Ceramedix: Honoraria; Rheos: Honoraria; Nektar: Honoraria; Priothera: Honoraria; Lygenesis: Honoraria; WindMIL: Honoraria; Wolters Kluwer: Patents & Royalties; Juno: Patents & Royalties; BeiGene: Consultancy; Kite: Consultancy; Magenta: Honoraria; Seres: Honoraria, Other: Stock, Patents & Royalties, Research Funding; PCYC: Consultancy; Notch: Honoraria, Other: Stock; Novartis: Consultancy; Pluto: Honoraria. Olszewski: Acrotech Pharma: Research Funding; Celldex Therapeutics: Research Funding; TG Therapeutics: Research Funding; PrecisionBio: Research Funding; Genentech, Inc.: Research Funding; Genmab: Research Funding. Trotman: PCYC: Research Funding; roche: Research Funding; BMS: Research Funding; TAKEDA: Research Funding; JANSSEN: Research Funding; beigene: Research Funding.

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Phase II Trial of Weekly Bortezomib in Combination with Rituximab in Untreated Patients with Waldenstrom's Macroglobulinemia.

Blood ◽

10.1182/blood.v114.22.3752.3752 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3752-3752

Author(s):

Irene M. Ghobrial ◽

Swaminathan Padmanabhan ◽

Ashraf Z. Badros ◽

Renee Leduc ◽

Meghan Rourke ◽

...

Keyword(s):

Herpes Zoster ◽

Board Of Directors ◽

Research Funding ◽

Waldenström’S Macroglobulinemia ◽

Advisory Committees ◽

Minor Response ◽

Waldenstrom's Macroglobulinemia ◽

A Minor ◽

Waldenström's Macroglobulinemia

Abstract Abstract 3752 Poster Board III-688 INTRODUCTION This study aimed to determine activity and safety of weekly bortezomib and rituximab in patients with untreated Waldenstrom's Macroglobulinemia (WM). Prior studies using twice a week bortezomib in this population showed high responses, but significant neuropathy. METHODS Patients who had symptomatic WM and were not previously treated were eligible. All patients received bortezomib IV weekly at 1.6 mg/m2 on days 1, 8, 15, q 28 days x 6 cycles, and rituximab 375 mg/m2 weekly on cycles 1 and 4. Dexamethasone was not added. Primary endpoint was the percent of patients with at least a minor response. Patients were encouraged to receive herpes zoster prophylaxis but it was not mandated. RESULTS Twenty-six patients were treated. At least minimal response or better was observed, assessed using serum protein electropheresis, in 24/26 cases (92%) with 2 patients (8%) in complete remission (CR)/near CR, 15 (54%) in partial response (PR), and 7(27%) in minimal response (MR). Two patients (8%) had stable disease. By using IgM by nephlometry, all 26 patients (100%) had at least a minor response, with 2 (8%) CR, 15 (58%) in PR and 9 (35%) with minor response. The median time of follow up is 11.2 months (range, 3-18.6). To date, six (23%) patients have developed progressive disease or required a new therapy. A single patient has died due to disease progression. The median progression-free survival and overall survival have not been reached. The most common grade 3 and 4 therapy related adverse events included anemia in 3 patients, lymphopenia in 2 patients; neutropenia, leucopenia, thrombocytopenia, pneumonia, fatigue, allergic reaction and nausea and vomiting in 1 patient for each. Five patients developed grade 2 peripheral neuropathy including 4 did who did not have neuropathy at baseline. It required dose reductions in cycles 4 and 5 and these neuropathies resolved to grade 1 or less with follow up. One case developed grade 1 herpes zoster reactivation in cycle 1. CONCLUSIONS The combination of weekly bortezomib and rituximab showed significant activity and minimal neurological toxicity in patients with untreated WM. Disclosures: Ghobrial: Millennium: Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Anderson:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Millennium: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Richardson:Keryx Biopharmaceuticals: Honoraria. Treon:Millennium: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Genentech: Honoraria, Research Funding, Speakers Bureau. Matous:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cephalon: Membership on an entity's Board of Directors or advisory committees.

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