Antigenic Variation of Hairy Cell Leukemia Defines a CD25 Negative Variant with a Uniform Immunophenotype and Distinct Clinicopathologic Features.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1102-1102
Author(s):  
Henry Y. Dong
Keyword(s):  
Flow Cytometry ◽  
Hairy Cell Leukemia ◽  
Standard Therapy ◽  
Overall Response Rate ◽  
Response Rate ◽  
Complete Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Overall Response

Abstract Classical hairy cell leukemia (HCL) coexpressing both CD25 and CD103 is highly responsive to the treatment with cladribine and pentostatin (complete response rate, 75–95%; overall response rate, 86–100%). HCL variant in the literature is characterized by HCL-like morphology, lack of CD25 coexpression, and variable immunophenotypes indistinguishable from those of splenic marginal zone B cell lymphoma (Matutes, et al. Leukemia2001; 15:184). Importantly, HCL variant is associated with a poor response to standard therapy. It is unclear if HCL cases lacking CD25 but otherwise phenotypically identical to classical HCL belong to HCL or HCL variant, and if the standard therapy is effective in these patients. To further delineate features of HCL and its variants, we analyzed immunophenotyping data, by flow cytometry or immunohistochemistry, or by both when feasible, in 260 consecutive patients with HCL (Dong, et al. Mod Pathol2003; 16:230A). The diagnosis was established by hairy cell morphology together with coexpression of strong CD20 and CD22, bright CD11c, and CD103. Clinical data were obtained for a subset of cases in which expression of CD25 was distinctly absent. Our results were consistent with the literature in that HCL has a consistent and unique immunophenotypic profile, which allowed detection of residual HCL by flow cytometry at levels as low as 0.1% of total cells. In addition, approximately 20% and 37% of classical HCL coexpressed CD10 and BCL-1 respectively, which may significantly confuse the diagnosis in an incomplete work-up. Interestingly, there were 43 cases (20% of all CD103+ cases) that lacked CD25 but were otherwise identical to classical HCL in their uniform phenotypic profiles. Compared with classical HCL, patients with the CD25- HCL were generally older (medium age: 59yrs vs. 79yrs; p=0.001) and frequently had leukocytosis (medium WBC: 3.0x109/L vs. 24.5x109/L; p=0.014). Among 14 patients with follow up data, 7 were treated with cladribine or pentostatin. The complete response (CR) rate was 14.3% (1/7) and the overall response rate was 57.1% (4/7). Three patients had no response. One patient who had an initial partial response (PR) to pentostatin died of the disease 10 months after the diagnosis. Of others, an additional two patients achieved CR and PR upon initial treatment with fludarabine and Rituxamab respectively. Four patients were untreated and were alive with disease (follow up, 21–41 months). One patient died of the disease in 2 years and treatment for this patient was unknown. These clinical features overlapped with those of HCL variant in the literature. However, unlike the HCL variant that has significant phenotypic heterogeneity, including lack of CD11c and CD103 in a substantial number of cases, the CD25- HCL was remarkably uniform in phenotype and can be easily identified by immunophenotyping. In conclusion, these results suggest that lack of CD25 in HCL defines a clinically distinct chronic lymphoproliferative disorder, which appears to require different clinical management.

Phase 2 Study of Ibrutinib in Classic and Variant Hairy Cell Leukemia

Blood ◽  
2021 ◽  
Author(s):  
Kerry A. Rogers ◽  
Leslie Ann Andritsos ◽  
Lai Wei ◽  
Eric McLaughlin ◽  
Amy S Ruppert ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hairy Cell Leukemia ◽  
Primary Outcome ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase 2 ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Overall Response ◽  
Phase 2 Study

Hairy cell leukemia is a rare B-cell malignancy where there is a need for novel treatments for patients who do not benefit from purine analogues. Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies. Its activity in HCL was unknown. Therefore, we conducted a multisite phase 2 study (NCT01841723) of oral ibrutinib in patients with either relapsed classic or variant hairy cell leukemia. The primary outcome measure was the overall response rate at 32 weeks with response at 48 weeks and best response during treatment also assessed. Key secondary objectives were characterization of toxicity and determination of progression-free and overall survival. Thirty-seven patients were enrolled (24 at 420mg, 13 at 840mg). The median duration of follow-up was 3.5 years (range 0-5.9). The overall response rate at 32 weeks was 24% which increased to 36% at 48 weeks. The best overall response rate was 54%. The estimated 36-month progression-free and overall survivals were 73% and 85%, respectively. The most frequent adverse events were diarrhea (59%), fatigue (54%), myalgia (54%), and nausea (51%). Hematologic adverse events were common with anemia (43%), thrombocytopenia (41%), and neutropenia (35%). Ibrutinib can be safely administered to hairy cell leukemia patients with objective responses and results in prolonged disease control. While the initial primary outcome objective of the study was not met, the observation of objective responses in heavily pretreated patients coupled with a favorable progression-free survival suggest that ibrutinib may be beneficial in these patients.

High Response Rate of Moxetumomab Pasudotox in Relapsed/Refractory Hairy Cell Leukemia Includes Eradication of Minimal Residual Disease: Potential Importance for Outcome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4161-4161 ◽  
Author(s):  
Robert J. Kreitman ◽  
Evgeny Arons ◽  
Martin S Tallman ◽  
Robak Tadeusz ◽  
Steven Coutre ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Hairy Cell Leukemia ◽  
Overall Response Rate ◽  
Response Rate ◽  
Residual Disease ◽  
Response Duration ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Multicolor Flow Cytometry ◽  
Purine Analog

Abstract Background: In patients with hairy cell leukemia (HCL), the clinical importance of minimal residual disease is unknown; particularly by bone marrow aspirate (BMA) multicolor flow cytometry. It is often assumed that agents failing to eradicate MRD may prove equally effective as those that do. Moxetumomab pasudotox is a recombinant immunotoxin containing truncated Pseudomonas exotoxin fused to an anti-CD22 Fv. After the dose-escalation phase of a phase I trial in 28 patients with relapsed/refractory HCL treated with 5-50 ug/Kg every other day for 3 doses (QOD x3), a complete remission (CR) rate of 46% and overall response rate (ORR) of 86% were reported. Two cases of reversible grade-2 hemolytic uremic syndrome (HUS) were also reported, with transient grade I platelet and creatinine changes. Methods: To determine response and toxicity at a fixed dose, Twenty-one additional patients were enrolled at the highest dose level, totaling 33 patients at 50 ug/Kg QOD x3 and 49 patients overall. Patients required at least 2 prior courses of purine analog, or 1 course each of purine analog and rituximab if response duration to the first purine analog was <2 years. CR criteria included absence of HCL cells by morphologic stains of bone marrow and blood. In CRs, multicolor flow cytometry was used to detect MRD in the BMA as well as blood. Results: No dose limiting toxicity or additional HUS cases were observed in any of the 202 cycles administered to 49 patients. Of 33 patients receiving 143 cycles of 50 ug/Kg QOD x3, the overall response rate was 88% and 21 (64%) achieved CR. Of 20 CRs followed for response duration, the median duration of CR (disease-free survival, DFS) was 42 mo (range 5 - 72), with 12 (60%) of 20 remaining in CR at a median of 42 mo. In addition to the 21 CRs achieved at 50 ug/Kg, there were 2 CRs out of 4 patients treated at 40 ug/Kg, and 5 CRs out of 12 patients treated at lower dose levels. Of the 28 CRs, MRD by BMA flow cytometry was evaluated in all except in 1 patient each at 50 and 40 ug/Kg, and 2 patients at lower doses. By BMA flow cytometry, MRD-negative CR was achieved in 11 (34%) of 32 at 50 ug/Kg, 1 of 3 at 40 ug/Kg, and 0 of 10 at lower doses (Fisher's Exact comparison above vs below 40 ug/Kg, p=0.041). MRD+ CRs included 9 at 50 ug/Kg, 0 at 40 ug/Kg, and 3 at lower doses. For the 12 MRD-negative CRs at 40-50 ug/Kg, DFS has not been reached, compared to a DFS of 17 mo in the 9 remaining MRD+ CRs at 40-50 ug/Kg (p<0.0001). Of the 12 MRD-negative CRs, 11 (92%) remain in CR at 16-79 (median 42) mo of follow-up. Conclusion: Moxetumomab pasudotox can eliminate HCL MRD, and MRD eradication significantly correlated with CR durability. In HCL, particularly after multiple relapses, CRs should optimally be achieved without MRD. To our knowledge, moxetumomab pasudotox is the only known agent capable of eliminating MRD in HCL in a high percentage of patients without causing myelosuppressive toxicities common to chemotherapy. Its activity and safety profile support multicenter pivotal phase III testing, which is currently ongoing. This summary contains investigator reported data. This study was sponsored by MedImmune and supported by NCI's Intramural Research Program and the Hairy Cell Leukemia Research Foundation. Disclosures Lanasa: MedImmune: Employment. FitzGerald:NIH: Patents & Royalties: Coinventor on NIH Patent. Pastan:NIH: Patents & Royalties: Coinventor on NIH Patent.

Long-Term Follow-Up of Patients With Hairy Cell Leukemia After Cladribine Treatment

Blood ◽  
1998 ◽  
Vol 92 (6) ◽  
pp. 1918-1926 ◽  
Author(s):  
Alan Saven ◽  
Carol Burian ◽  
James A. Koziol ◽  
Lawrence D. Piro
Keyword(s):  
Hairy Cell Leukemia ◽  
Survival Rates ◽  
Complete Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Second Neoplasms ◽  
American Society ◽  
La Jolla

Abstract Hairy cell leukemia is a chronic B-cell disorder that follows an indolent, but progressive course. Cladribine (2-chlorodeoxyadenosine) induces complete remissions in the majority of patients after a single course. We report the long-term outcomes, including response rates and their duration; time-to-treatment failure (TTF) rates; retreatment results; toxicities; and survival rates of patients treated at Scripps Clinic (La Jolla, CA). A total of 358 patients with hairy cell leukemia were treated with cladribine at 0.087 or 0.1 mg/kg body weight per day by continuous intravenous infusion for 7 days. The expected number of second neoplasms was based on the National Cancer Institute’s Surveillance Epidemiology and End Results data. Of 349 evaluable patients, 319 (91%) achieved an initial complete response and 22 (7%) a partial response with an overall median duration of response follow-up of 52 months. Ninety patients (26%) had relapsed at a median of 29 months. The TTF rate for all 341 responders was 19% at 48 months, 16% for complete responders, and 54% for partial responders. Of 53 evaluable patients treated with second courses of cladribine at first relapse, 33 (62%) achieved complete responses and 14 (26%) partial responses. Twenty-seven patients (8%) developed second neoplasms (only 1 hematopoietic) with an observed-to-expected ratio of 1.88 (95% confidence interval, 1.24 to 2.74). The overall survival rate was 96% at 48 months. Single courses of cladribine induced long-lasting complete responses in the vast majority of patients. Relapse rates for complete responders were low. Patients who relapse can be successfully retreated with cladribine. Cladribine has high efficacy and a favorable acute and long-term toxicity profile when administered to patients with hairy cell leukemia. © 1998 by The American Society of Hematology.

scholarly journals Vemurafenib Has Potent Antitumor Activity in Patients with Relapsed/Refractory BRAF Mutant Hairy Cell Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 24-24
Author(s):  
Jae H Park ◽  
Stephen S. Chung ◽  
Young Rock Chung ◽  
Helen Won ◽  
Eunhee Kim ◽  
...  
Keyword(s):  
Map Kinase ◽  
Hairy Cell Leukemia ◽  
Response Rate ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Purine Analogs ◽  
Promising Therapeutic Target ◽  
Map Kinase Pathway ◽  
Braf Mutant

Abstract Background: Although treatment with purine analogs is associated with a high response rate, hairy cell leukemia (HCL) remains incurable with a 30-40% relapse rate. For these patients (pts) and those intolerant to purine analogs, novel therapies are needed. The major finding that BRAFV600E mutations occur in 98% of HCL suggests BRAF as a promising therapeutic target. We therefore designed a phase II trial to (1) determine the clinical efficacy of the BRAF inhibitor vemurafenib in pts with relapsed/ refractory HCL and (2) identify biologic determinants of response and resistance to vemurafenib in HCL. Patients and Methods: Pts with BRAF mutant HCL who were refractory or resistant to purine analogs, or who had ≥2 relapses with an indication for treatment (ANC ≤1.0, HGB ≤10, or PLT ≤100K) were enrolled. Eligible pts received vemurafenib 960mg twice daily for 3 months. Bone marrow (BM) evaluations were performed after 3 months to assess response. Pts with partial (PR) or complete response (CR) with detectable minimal residual disease (MRD) were allowed to receive vemurafenib for up to 3 additional months. The primary endpoint of the study was overall response rate (ORR: CR + PR). Using a Simon’s mini-max two-stage design, if at least 4 of the 19 pts (≥20%) achieve ORR in the first stage, an additional 17 patients will be accrued to the second stage. If 11 or more pts achieve ORR out of the 36 pts, the study would be considered worthy of further investigation. Serial peripheral blood and/or BM samples were collected during the study for quantitative BRAF mutant allele burden, serum cytokine, multiparameter flow cytometry, and targeted next-generation sequencing analysis of a 350-gene panel to detect potential predictors of resistance and identify genes collaborating with BRAF mutations in HCL. Results: 22 pts have been enrolled and 20 pts received treatment. The median age was 61 years (range 44-77), and the median number of prior treatments was 3.5 (range 1-7). 20 pts are evaluable for toxicity and 17 patients for disease response with a median follow up of 10 months (range 2-19). The most common adverse events were rash (40%, Gr1-2), arthralgia (30%, Gr1-2), photosensitivity (20%, Gr1), and pruritis (15%, Gr1). Three pts developed squamous cell carcinoma (SCC), all of whom had previous history of SCC. All patients were able to complete the intended treatment (3 cycles: 11 pts, >3 cycles: 6 pts). All 17 evaluable pts achieved complete hematologic recovery with an overall response rate (ORR) of 100%. 6 pts achieved CR (4 MRD- and 2 MRD+) and 11 pts achieved PR with very minimal disease (Figure 1). Responses were rapid with reduction of circulating hairy cells within 24 hours and normalization of sCD25 within 2-3 weeks (Figure 2). This correlated with dephosphorylation of ERK at 1 month. Several additional inflammatory cytokines correlated with the leukemic cell burden identifying novel tumor markers in HCL including sTNF-R2, sIL-1R2, and sIL4R. Genetic analysis identified a median of 3 (range 0-5) somatic mutations co-existing with the BRAFV600E mutation in HCL including recurrent mutations in MLL2 and CREBBP (Figure 2). Several of these alterations were present as minor clones identifying a clonal architecture in HCL which was not previously appreciated. One pt was found to have de novo resistance to vemurafenib. Genetic analysis identified that this pt’s pretreatment HCL cells harbored a previously undescribed missense mutation in IRS1 (IRS1P1201S) in addition to BRAFV600E mutation. Given prior knowledge that IRS1 (Insulin Receptor Substrate 1) activates both MAP kinase and PI3K-AKT signaling, we compared the effects of expression of wildtype and mutant IRS1 cDNAs on signaling. This revealed robust activation of PI3K-AKT signaling induced by IRS1P1201S-mutant cells relative to wildtype. Conclusions: While longer follow-up is needed to assess the durability of the response, our results indicate that vemurafenib has potent antitumor activity in pts with relapsed/refractory BRAF mutant HCL. These data confirm the MAP kinase pathway as a rational promising therapeutic target in HCL and identify activation of signaling pathways parallel to the MAP kinase pathway as a first mechanism of RAF inhibitor resistance in a hematological malignancy. Subsequent studies will be required to prove that inhibition of B-raf may be the best initial therapy in HCL pts who require treatment. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Park: Genentech: Research Funding. Off Label Use: Vemurafenib in hairy cell leukemia. Rosen:Novartis: Consultancy.

Long-Term Follow-Up of Patients With Hairy Cell Leukemia After Cladribine Treatment

Blood ◽  
1998 ◽  
Vol 92 (6) ◽  
pp. 1918-1926 ◽  
Author(s):  
Alan Saven ◽  
Carol Burian ◽  
James A. Koziol ◽  
Lawrence D. Piro
Keyword(s):  
Hairy Cell Leukemia ◽  
Survival Rates ◽  
Complete Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Second Neoplasms ◽  
American Society ◽  
La Jolla

Hairy cell leukemia is a chronic B-cell disorder that follows an indolent, but progressive course. Cladribine (2-chlorodeoxyadenosine) induces complete remissions in the majority of patients after a single course. We report the long-term outcomes, including response rates and their duration; time-to-treatment failure (TTF) rates; retreatment results; toxicities; and survival rates of patients treated at Scripps Clinic (La Jolla, CA). A total of 358 patients with hairy cell leukemia were treated with cladribine at 0.087 or 0.1 mg/kg body weight per day by continuous intravenous infusion for 7 days. The expected number of second neoplasms was based on the National Cancer Institute’s Surveillance Epidemiology and End Results data. Of 349 evaluable patients, 319 (91%) achieved an initial complete response and 22 (7%) a partial response with an overall median duration of response follow-up of 52 months. Ninety patients (26%) had relapsed at a median of 29 months. The TTF rate for all 341 responders was 19% at 48 months, 16% for complete responders, and 54% for partial responders. Of 53 evaluable patients treated with second courses of cladribine at first relapse, 33 (62%) achieved complete responses and 14 (26%) partial responses. Twenty-seven patients (8%) developed second neoplasms (only 1 hematopoietic) with an observed-to-expected ratio of 1.88 (95% confidence interval, 1.24 to 2.74). The overall survival rate was 96% at 48 months. Single courses of cladribine induced long-lasting complete responses in the vast majority of patients. Relapse rates for complete responders were low. Patients who relapse can be successfully retreated with cladribine. Cladribine has high efficacy and a favorable acute and long-term toxicity profile when administered to patients with hairy cell leukemia. © 1998 by The American Society of Hematology.

Cyclophosphamide Remains An Important Component of Treatment in CLL Patients Receiving Pentostatin and Rituximab Based Chemoimmunotherapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 43-43 ◽  
Author(s):  
Neil E. Kay ◽  
Wenting Wu ◽  
John C. Byrd ◽  
Brian Kabat ◽  
Diane F. Jelinek ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Patient Characteristics ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Overall Response ◽  
Grade 3 ◽  
Ecog Ps ◽  
Experienced Grade

Abstract BACKGROUND: We have previously studied and reported that the combination of pentostatin (P, 2 mg/m2), cyclophosphamide (C 600 mg/m2) and rituximab (R 375 mg/m2) in previously untreated CLL is highly effective with an overall response (OR) rate of over 90% and a complete response rate (CR) of 41% (Blood109:405–411, 2007). We also found that this regimen can be effective even in older patients (&gt;70 y), those with elevated beta-2 microglobulin levels, and patients with mildly reduced creatinine clearances (Cancer. 109:2291–2298, 2007). To determine whether similar benefit could be achieved without inclusion of an alkylating agent, we conducted a follow-up trial testing pentostatin and rituximab without cyclophosphamide and employing a higher pentostatin dose (4 mg/m2). METHODS: Eligible pts had documentation of active CLL by standard NCI-WG criteria, and were previously untreated. Treatment schema consisted of 6 cycles of pentostatin (4 mg/m2) and rituximab given every 21 days. Pentostatin was given on the first day of each cycle following infusion of rituximab. Rituximab was given at 100mg/m2 IV at day 1, then 375 mg/m2 IV on days 3 and 5 of the first treatment cycle. During cycles 2 to 6, Rituximab was given at 375 mg/m2 as a single IV infusion day 1 of week 4, 7, 10, 13 and 16. All patients were staged two months after completion of the 6 cycles of PR using the NCI-WG criteria. PATIENT CHARACTERISTICS: Overall, 33 patients were enrolled at Mayo Clinic and Ohio State University between July 2005 and February 2008. All 33 were eligible: 82% male, median age 65 (range: 45–81), with 9 (27%) being 70 years or older. 76% had a baseline ECOG PS of 0, and the rest were ECOG PS 1. Overall, 36% of patients had intermediate Rai risk (stage I–II) and 63% high Rai risk (stage 3–4) disease. Prognostic testing revealed that 36% were CD38+, 50% were Zap-70 +, and 39% had an unmutated IgVh status. Chromosome analysis by FISH found that 99% had detectable FISH panel defect, including 61%, 27% and 3% of patients with 1, 2, or 3 FISH detects, respectively. RESULTS: 28 of 33 patients (85%) completed therapy. While on treatment, 6 pts (18%) had a dose held or modified with 4 of these delays due to hematologic AE. For adverse events deemed at least possibly related to treatment, 4 (12%) pts experienced grade 3+ hematologic toxicity and 5 (15%) experienced grade 3+ non-hematologic toxicity. Out of all 33 enrolled patients, the overall response rate was 79% with 10 CR, 6 nPR, and 10 PR. At the time of this analysis, 29/33 patients are still alive with a median follow-up time of 14 months on surviving patients. To date 17/33 (52%) of patients have progressed with an estimated median time to progression of 12 months (95% CI: 8.5–21 months). 13/26 responders have progressed. Median duration of response is 12.5 months ((95% CI: 11–21 months). Finally, since eligibility were nearly identical and enrollment accrued at the same two academic centers, we compared the patient characteristics, response rates, and PFS of the 33 patients treated with PR to the 64 patients previously treated on our PCR trial. Patients in the two studies were generally similar with respect to demographic and prognostic characteristics, although patients in the PR trial had higher WBC and were less likely to be IgVH unmutated (Table). Although the differences in ORR and CR rate were not significantly different, the PFS appeared to be inferior in patients treated with PR as compared to PCR (12 months vs. 31 months; p=0.003). CONCLUSION: Although the PR regimen achieves a high OR response rate, the PFS appears inferior to PCR therapy. These findings suggest that increasing the purine nucleoside analogue dose does not eliminate the need to include cyclophosphamide in chemoimmunotherapy for patients with CLL. PCR Trial N=64 PR Trial N=33 P value Age, median(range) 63 years (38–80) 65 years (45–81) 0.34 ≥70 years(%) 28% 27% Male 77% 82% 0.61 Rai stage 0 5% 0 0.46 Rai stage I–II 42% 36% Rai stage III–IV 53% 64% White Cell Count, median(range) 79 × 109/L (11–519) 127 × 109/L (8–430) 0.04 &lt;50 × 109/L 36% 28% 50–149 × 109/L 44% 25% &gt;150 × 109/L 20% 47% Serum B2-microglobulin, median(range) 3.97 (1.8–13.5) 3.80 (2.0–8.2) 0.81 &gt;2 × Upper Limit Normal(%) 57% 58% CD38 Positive 34% 36% 1.00 ZAP-70 Positive 36% 50% 0.26 IgVH Unmutated 71% 39% 0.004 FISH Normal, 11% 9% 13q- 35% 42% +12 21% 24% 6q- 2% 0 11q- 22% 18% 17p- 6% 3% other 3% 3% Overall Response Rate 91% 79% 0.12 Complete Response Rate 41% 30% 0.38 Median PFS 31 months 12 months 0.003

Brentuximab Vedotin Followed By ABVD in Patients with Previously Untreated Hodgkin Lymphoma. a Pilot Phase II Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3088-3088 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Stefano Luminari ◽  
Francesco Merli ◽  
Emanuela Anna Pesce ◽  
Stephane Chauvie ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Complete Response ◽  
Pilot Phase ◽  
First Line ◽  
Overall Response

Abstract active and well tolerated single agent in the treatment of heavily pretreated Hodgkin lymphoma patients. In this pilot phase II study patients with previously untreated HL underwent sequential regimen consisting in 2 cycles of BV before doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) +/- radiotherapy (RT). The primary endpoint of the study was the response to BV assessed by positron emission tomography (PET) after the 2 cycles (PET2), defined as reduction of Deauville score or, in case of no change in Deauville score, as any reduction in standard uptake value (SUV) intensity compared to basal SUV. Between April and October 2013, 12 patients with a median age at diagnosis of 36 years (range, 19-70), 11 stage I-IIA and 1 stage IIIA, were enrolled. BV was administered as scheduled and at the full dose of 1.8 mg/kg in all patients. After the 2 cycles of BV, the overall response rate was 91%, comprising of ten (83%) complete responses and one (8%) partial metabolic response. The non responding patient had stage III and showed a new lesion at PET2. After ABVD +/- RT, the overall response rate was 100% with 11 complete responses and 1 partial response (converting from progression disease). At a median follow up of 8 months, all 11 patients are still in complete response, while the remaining one relapsed. During BV therapy, the only grade 3 adverse events were transient and asymptomatic increase in liver transaminases (n=3, 25%) and gamma glutamyl transpeptidase (n=2, 17%). During ABVD +/- RT grade III-IV neutropenia occurred in 9 (75%) patients. All toxicities were transient and resolved with growth factor support. Two cycles of BV as first line-treatment in limited stage HL induced an outstanding complete response rate with limited toxicity and reducing the need of chemotherapy. Waiting for a longer follow up to assess the duration of response, our data (sequential administration of immunotherapy and chemotherapy) should be considered the starting point for further studies in first line therapy for limited stage HL patients. Disclosures No relevant conflicts of interest to declare.

Durability of complete remission by moxetumomab pasudotox (HA22 or CAT-8015) assessed by clone-specific real-time quantitative PCR (RQ-PCR).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2503-2503
Author(s):  
Robert J. Kreitman ◽  
Evgeny Arons ◽  
Jeffrey Sapolsky ◽  
Laura Roth ◽  
Hong Zhou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Real Time ◽  
Quantitative Pcr ◽  
Hairy Cell Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Real Time Quantitative Pcr ◽  
Recombinant Immunotoxin

2503^ Background: The anti-CD22 recombinant immunotoxin moxetumomab pasudotox, also known as HA22 or CAT-8015, was recently reported in phase I testing to achieve complete remissions (CRs) in 13 (46%) of 28 patients with relapsed/refractory hairy cell leukemia (HCL); 3 of 13 patients have relapsed. Methods: To complete this trial, 20 additional patients received the highest dose level (50 µg/Kg every other day x 3 doses); none of the 48 HCL patients had dose-limiting toxicity (DLT). Results: Of the first 42 patients with >6 mo of follow up off-treatment, 23 (55%) had CRs, with an overall response rate of 88%. Of the 23 CRs, 21 were evaluable for minimal residual disease (MRD) using flow cytometry of blood and immunohistochemistry of the bone marrow biopsy, and 17 (81%) were negative. Of these 17 patients, 11 (65%) were negative by bone marrow aspirate (BMA) flow cytometry. PCR using consensus primers for the heavy chain immunoglobulin (IgH) rearrangement was less specific than flow cytometry of blood, since IgH rearrangements of normal B cells, which recovered rapidly after immunotoxin treatment, were also amplified. For better MRD detection in blood, patient IgH sequences were cloned and sequence specific primers and probes designed for real-time quantitative PCR (RQ-PCR). RQ-PCR of blood was negative in 6 (100%) of 6 patients achieving flow-negativity in both blood and BMA and positive in 3 (100%) of 3 patients flow-negative in blood but not BMA (p=0.01). No relapses from CR have been observed in 10 patients who became RQ-PCR-negative in blood or flow-negative in BMA, with 5-38 (median 11) mo of follow-up. Conclusions: We conclude that clone-specific RQ-PCR is the most sensitive blood test for MRD in our HCL patients after moxetumomab pasudotox, and could be used to assess the possibility of long-term molecular remissions. We believe these results, including durable CRs without DLT, support a pivotal trial in which moxetumomab pasudotox is compared with alternative therapy. Note: this summary contains investigator reported data. This study was funded by MedImmune, LLC, and supported by NCI’s Intramural Research Program and the Hairy Cell Leukemia Research Foundation.

Pentostatin induces durable remissions in hairy cell leukemia.

1991 ◽  
Vol 9 (2) ◽  
pp. 243-246 ◽  
Author(s):  
P A Cassileth ◽  
B Cheuvart ◽  
A S Spiers ◽  
D P Harrington ◽  
F J Cummings ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Overall Response Rate ◽  
Disease Free Survival ◽  
Maximal Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Free Survival ◽  
Disease Free

Fifty patients with hairy cell leukemia were treated with pentostatin (2'-deoxycoformycin; dCF) for a median of 3 months; 32 (64%) patients achieved complete remission (CR), and 10 (20%) patients achieved partial remission (PR), for an overall response rate of 84%. After reaching maximal response, no maintenance therapy was administered. The median duration of follow-up is now 39 months, and only four of 32 patients in CR and two of 10 patients in PR have relapsed. dCF therapy produces durable long-term, disease-free survival in patients with hairy cell leukemia.

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