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

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.

scholarly journals 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

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.

Waldenström’s Macroglobulinemia: Clinical Features, Complications, and Management

2000 ◽  
Vol 18 (1) ◽  
pp. 214-214 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Panayiotis Panayiotidis ◽  
Lia A. Moulopoulos ◽  
Petros Sfikakis ◽  
Marinos Dalakas
Keyword(s):  
Clinical Features ◽  
Nucleoside Analogs ◽  
Low Grade ◽  
Waldenström’S Macroglobulinemia ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
The Impact ◽  
Waldenström's Macroglobulinemia

PURPOSE: To review the clinical features, complications, and treatment of Waldenström’s macroglobulinemia, a low-grade lymphoproliferative disorder that produces monoclonal immunoglobulin (Ig) M. METHODS: A review of published reports was facilitated by the use of a MEDLINE computer search and by manual search of the Index Medicus. RESULTS: The clinical manifestations associated with Waldenström’s macroglobulinemia can be classified according to those related to direct tumor infiltration, to the amount and specific properties of circulating IgM, and to the deposition of IgM in various tissues. Asymptomatic patients should be followed without treatment. For symptomatic patients, standard treatment consists primarily of oral chlorambucil; nucleoside analogs, such as fludarabine and cladribine, are effective in one third of previously treated patients and in up to 80% of previously untreated patients. Preliminary evidence suggests that anti-CD20 monoclonal antibody may be active in about 30% of previously treated patients and that high-dose therapy with autologous stem-cell rescue is effective in most patients, including some with resistance to nucleoside analogs. CONCLUSION: Waldenström’s macroglobulinemia has a wide clinical spectrum that practicing physicians need to recognize early to reach the correct diagnosis. When therapy is indicated, oral chlorambucil is the standard primary treatment, but cladribine or fludarabine can be used when a rapid cytoreduction is desirable. Prospective randomized trials are required to elucidate the impact of nucleoside analogs on patients’ survival. A nucleoside analog is the treatment of choice for patients who have been previously treated with an alkylating agent.

Combination chemotherapy (M-2) protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone) for Waldenstrom macroglobulinemia: preliminary report

Blood ◽  
1982 ◽  
Vol 59 (5) ◽  
pp. 934-937 ◽  
Author(s):  
DC Jr Case
Keyword(s):  
Combination Chemotherapy ◽  
Response Rate ◽  
Waldenström’S Macroglobulinemia ◽  
Symptomatic Disease ◽  
Previously Treated ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Initiation Of Therapy ◽  
Waldenström's Macroglobulinemia

Abstract Fourteen consecutively referred, symptomatic patients with Waldenstrom's macroglobulinemia (ages 52–87 yr) have been treated with the 5-drug M-2 protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone). Three patients were previously treated and 11 patients were untreated. The majority of patients were symptomatic from hyperviscosity. All patients have responded to therapy. Two patients have achieved complete remissions and 12 patients partial remissions to date. None of the patients with symptomatic hyperviscosity has required plasmapheresis since therapy with the M-2 has been initiated. Lymphadenopathy, hepatosplenomegaly, and anemia have also responded to treatment. Follow-up data are limited, with survival from initiation of therapy with the M-2 ranging from 2+ to 35% mo (median 17+ mo) 2+-40+ mo from time of diagnosis). Combination chemotherapy for Waldenstrom's macroglobulinemia with the M-2 protocol appears to increase the response rate in patients with symptomatic disease. Further survival analysis will be carried out.

Sildenafil citrate suppresses disease progression in patients with Waldenstrom’s macroglobulinemia

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7556-7556 ◽  
Author(s):  
C. J. Patterson ◽  
J. Soumerai ◽  
Z. Hunter ◽  
X. Leleu ◽  
I. Ghobrial ◽  
...  
Keyword(s):  
Disease Progression ◽  
Maximum Tolerated Dose ◽  
Preliminary Evidence ◽  
Response To Therapy ◽  
Sildenafil Citrate ◽  
Waldenström’S Macroglobulinemia ◽  
Minor Response ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

7556 Background: Responses to sildenafil citrate (Viagra), a phosphodiesterase-5 inhibitor used to treat erectile dysfunction, have been observed in patients with Waldenstrom’s Macroglobulinemia (WM). Moreover, sildenafil citrate induces apoptosis of WM lymphoplasmacytic cells (Clin Lymphoma 5:205, 2004). We therefore conducted a prospective phase II study of sildenafil citrate in patients with slowly progressing WM who did not meet consensus eligibility for active therapy (Semin Oncol 2003; 30:116). Intended therapy was as follows: Week 1 25 mg po qD Week 2 50 mg po qD Week 3 75 mg po qD Week 4, then Months 2–24 100mg po qD or Maximum Tolerated Dose Methods: Thirty patients were enrolled, 18 of whom were previously untreated. All patients demonstrated progressing disease prior to enrollment. Median age was 66 (range 43–85 yrs), baseline BM involvement was 30% (range 5–90%), serum IgM was 3,640 (range 790–6,720 mg/dL), hematocrit was 37.1% (range 32.7–58.5%), and B2M was 2.3 (range 1.5–8.9 mg/dL). Patients were evaluable for response after 3 months of therapy. Results: At a median of 3 months, serum IgM levels declined in 19/30 (63%) patients from a median of 3,640 (range 790–6,720 mg/dL) to 2,965 (range 1,170–6,110 mg/dL). 5/30 patients (17%) demonstrated at least a minor response (≥25% IgM decrease). Two patients were taken off study for non-response to therapy. Toxicities were mild and included headaches, sinus congestion, facial flushing, dyspepsia, and generally resolved on their own with prolonged sildenafil citrate usage. Only two patients required dose modification to 25 mg and 75 mg po qD, respectively. Corollary studies to determine putative mechanisms of action for sildenafil citrate in WM were also performed and will be updated at the meeting. Conclusions: This prospective clinical trial provides preliminary evidence for activity of sildenafil citrate in patients with advancing WM. With minimal toxicity, sildenafil citrate appears to have suppressed disease progression in more than half of patients and has resulted in objective responses, thus warranting further investigation in WM and possibly other B-cell disorders. No significant financial relationships to disclose.

Enzastaurin in Previously Treated Waldenstrom's Macroglobulinemia: An Open-Label, Multicenter, Phase II Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3867-3867
Author(s):  
Irene M Ghobrial ◽  
Jean-Luc Harousseau ◽  
Steven P Treon ◽  
Brianna Harris ◽  
Courtney E Lin ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Phase Ii ◽  
Waldenström’S Macroglobulinemia ◽  
Two Stage ◽  
Advisory Committees ◽  
Minor Response ◽  
Previously Treated ◽  
Grade 3 ◽  
A Minor ◽  
Waldenström's Macroglobulinemia

Abstract Abstract 3867 Poster Board III-803 Background Enzastaurin is an oral serine/threonine kinase inhibitor that targets the PKC and PI3K/AKT pathways. Enzastaurin has demonstrated activity in preclinical models of multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM), and clinical studies suggest encouraging activity and a well-tolerated safety profile in a variety of hematologic cancers. We are conducting a multicenter, two (parallel) cohort, two-stage, phase II trial to determine whether further study of single-agent enzastaurin is warranted in patients with previously treated WM or MM. The primary objective is to assess the response rate (RR); secondary objectives include assessment of time to progression (TTP), safety, biomarkers, and the impact of adding dexamethasone to enzastaurin in patients with progressive disease (PD). Preliminary results for the WM cohort are reported here. Methods Eligible patients with WM and 1-5 prior therapies were enrolled and treated with 250 mg oral enzastaurin twice daily (1125-mg loading dose on day 1) in 28-day cycles. Patients continued for 8 cycles or until PD or unacceptable toxicity occurred. At the investigator's discretion, dexamethasone (20-40 mg po QD, days 1-4, 9-12, and 17-20 for 4 cycles; days 1-4 of each cycle thereafter) was added to enzastaurin in patients with PD. According to the Simon two-stage design, if 2 of the first 10 patients (in stage 1) experienced a minor response (MR) or better, then the study would be expanded to 29 patients (stage 2). Best response was determined according to the response assessment recommendations of the Third International Workshop on WM (IWWM). Adverse events were graded according to CTCAE version 3.0. Results Twenty-nine patients (7 females, 22 males) with WM were enrolled. The median age was 65.6 years (range: 51.7-82.3 years) and 93% of patients had an Eastern Cooperative Oncology Group performance status of 0. Patients had a median of 2 prior systemic therapies and 26 patients (89.7%) had prior rituximab. Patients completed a median of 4 cycles. Six patients received ≥6 cycles of enzastaurin treatment. Twenty patients remain on study. There were no drug-related discontinuations. None of the patients had a complete response (CR). One patient had a partial response (PR) and 7 patients had a minor response (MR), for a RR (CR+PR+MR) of 27.6%. Immunoglobulin M decreased by ≥25% in 11 patients. Three (10.3%) patients had a PD. One patient had a drug-related grade 3 wound complication; there were no other drug-related grade ≥3 toxicities. One patient died on study due to infection unrelated to enzastaurin. Conclusions Although the results are preliminary, enzastaurin appears to have activity and is well tolerated in patients with previously treated WM. The WM cohort was expanded to allow up to 50 patients to be treated on study. Disclosures: Ghobrial: Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Honoraria, Research Funding, Speakers Bureau. Lin:Eli Lilly and Company: Employment. Yuan:Eli Lilly and Company: Employment. Benhadji:Eli Lilly and Company: Employment. Wooldridge:Eli Lilly and Company: Employment. Leblond:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria.

Bendamustine-Based Therapy Is Highly Active In Patients with Relapsed or Refractory Waldenstrom's Macroglobulinemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4700-4700
Author(s):  
Steven P. Treon ◽  
Christina Hanzis ◽  
Christina Trispsas ◽  
Leukothea Ioakimidis ◽  
Christopher Patterson ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
B Cell Lymphoma ◽  
Response Rates ◽  
Nucleoside Analogues ◽  
Waldenström’S Macroglobulinemia ◽  
Previously Treated ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Abstract Abstract 4700 Background: Waldenstrom's macroglobulinemia (WM) is an indolent B-cell malignancy characterized by lymphoplasmacytic cell infiltration of the bone marrow and production of an IgM monoclonal protein. Despite advances in treatment, WM remains incurable and novel agents are needed for ongoing disease control. Bendamustine represents an important novel agent for the treatment of B-cell disorders whose activity in WM remains to be clarified. Patients and Methods: We examined the outcome of 30 previously treated patients with the clinicopathological diagnosis of WM who received bendamustine-based therapy. The median prior therapies was 2 (range 1–9), and 16 (53%) patients were refractory to their previous treatment. Baseline characteristics for all patients: Median BM involvement 60%; serum IgM 3,980 mg/dL; Hct 31.0%; serum B2M 3.5 g/L. Treatment consisted of bendamustine administered at 90 mg/m2 IV on days 1, 2 as part of a 4 week cycle, along with rituximab (375 mg/m2 IV) given once on either day 1 or 2 for 24 patients. In the remainder 6 patients, severe rituximab intolerance prevented re-administration of rituximab. In these patients, bendamustine was either administered alone (n=4) or with ofatumumab (1000 mg IV) given on day 1 (n=2) following a test dose of 300 mg IV on day -7 prior to cycle 1 only. Intended therapy consisted of 4–6 cycles of treatment. Plasmapheresis was performed prior to treatment in patients exhibiting symptomatic hyperviscosity, or who had an IgM level >5,000 mg/dL and were to receive monoclonal antibodies in order to prevent a symptomatic IgM flare. Responses were assessed using modified WM consensus criteria, and patients were eligible for response assessment if they completed > 2 cycles of therapy. Results: 21 patients completed intended therapy; 9 patients continue on treatment. The median number of treatment cycles for all patients is 4 (range 2–6). Following treatment, median serum IgM levels declined from 3,980 to 1,210 mg/dL (p<0.0001), and hematocrit rose from 31.9% to 34.7% (p=0.005) at best response. The overall and major response rates were 80% and 73%, respectively, with 3 VGPR; 19 PR; 2 MR. 6 patients were non-responders. Responders included those patients receiving bendamustine alone (4 PR), or with ofatumumab (1 PR; 1 MR). With a median follow-up of 5 months, 22/24 responders continue in response. Overall, treatment was well tolerated with grade <2 nausea and diarrhea being the most common toxicities encountered. Three patients developed superficial thrombophlebitis at the site of bendamustine infusion, warranting institution of anticoagulation in 1 patient. Prolonged myelosuppression occurred in 3 patients who received previous nucleoside analogue therapy. One patient previously treated with nucleoside analogues and cyclophosphamide developed MDS, and another patient who received previous cyclophosphamide and bortezomib based therapies transformed to diffuse large B-cell lymphoma following bendamustine-based therapy. Conclusion: Bendamustine-based therapy is active in patients with relapsed or refractory WM and produces high response rates and durable responses both as monotherapy, and in combination with CD20 directed monoclonal antibodies. In patients previously treated with nucleoside analogues, prolonged myelosuppression may occur. Long term toxicities of bendamustine-based therapy remain to be clarified in this patient population. Disclosures: No relevant conflicts of interest to declare.

Ibrutinib in Previously Treated Waldenström’s Macroglobulinemia

2015 ◽  
Vol 372 (15) ◽  
pp. 1430-1440 ◽  
Author(s):  
Steven P. Treon ◽  
Christina K. Tripsas ◽  
Kirsten Meid ◽  
Diane Warren ◽  
Gaurav Varma ◽  
...  
Keyword(s):  
Waldenström’S Macroglobulinemia ◽  
Previously Treated ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

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

Blood ◽  
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.

scholarly journals Combination chemotherapy (M-2) protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone) for Waldenstrom macroglobulinemia: preliminary report

Blood ◽  
1982 ◽  
Vol 59 (5) ◽  
pp. 934-937
Author(s):  
DC Jr Case
Keyword(s):  
Combination Chemotherapy ◽  
Response Rate ◽  
Waldenström’S Macroglobulinemia ◽  
Symptomatic Disease ◽  
Previously Treated ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Initiation Of Therapy ◽  
Waldenström's Macroglobulinemia

Fourteen consecutively referred, symptomatic patients with Waldenstrom's macroglobulinemia (ages 52–87 yr) have been treated with the 5-drug M-2 protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone). Three patients were previously treated and 11 patients were untreated. The majority of patients were symptomatic from hyperviscosity. All patients have responded to therapy. Two patients have achieved complete remissions and 12 patients partial remissions to date. None of the patients with symptomatic hyperviscosity has required plasmapheresis since therapy with the M-2 has been initiated. Lymphadenopathy, hepatosplenomegaly, and anemia have also responded to treatment. Follow-up data are limited, with survival from initiation of therapy with the M-2 ranging from 2+ to 35% mo (median 17+ mo) 2+-40+ mo from time of diagnosis). Combination chemotherapy for Waldenstrom's macroglobulinemia with the M-2 protocol appears to increase the response rate in patients with symptomatic disease. Further survival analysis will be carried out.

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

Blood ◽  
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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