HSR19-086: Healthcare Costs and Resource Utilization Associated With Adverse Events Among Hairy Cell Leukemia Patients Treated With Purine Nucleoside Analogs

2019 ◽  
Vol 17 (3.5) ◽  
pp. HSR19-086
Author(s):  
Narendranath Epperla ◽  
Melissa Pavilack ◽  
Temitope Olufade ◽  
Richa Bashyal ◽  
Teng Huang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Resource Utilization ◽  
Hairy Cell Leukemia ◽  
Opportunistic Infections ◽  
Nucleoside Analogs ◽  
Purine Nucleoside ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
History Of

Background: Purine nucleoside analogs (PNAs) are highly effective for first-line treatment of hairy cell leukemia (HCL). In clinical trials of single PNAs, several adverse events (AEs) were reported; however, little is known regarding the costs and healthcare resource utilization (HRU) resulting from AEs in HCL patients (pts) treated with PNAs in non-clinical trial settings. Objective: Determine the costs and HRU of high incident and clinically important AEs associated with PNA therapy in HCL pts in the Truven MarketScan database. Methods: Adults (aged ≥18 years) with ≥2 HCL diagnosis codes ≥30 days apart during January 1, 2006–December 31, 2015 were included. Pts had ≥1 prescription claim for a PNA (cladribine or pentostatin ± rituximab) after HCL diagnosis date. First PNA claim date was defined as the index date. Pts had continuous health plan enrollment for ≥6 months at baseline and ≥12-months follow-up with no PNA in the baseline period. Pts were placed into cohorts based on the occurrence of myelosuppression (MSPN) and opportunistic infections (OI) as these were highest incident and clinically important AEs observed. Generalized linear models were used to compare outcomes during the 12-month follow-up. Results: Of the 219 pts with no history of MSPN, 101 developed MSPN (incidence [I]: 461 per 1000 pt-years) and of 619 pts with no history of OI, 26 developed OI (I: 42 per 1000 pt-years). Demographics were similar between pts with and without MSPN and OI. Pts who developed OI or MSPN had significantly higher inpatient admissions and costs (Table 1). Conclusions: PNA-treated HCL pts who developed MSPN or OI incurred higher HRU than those who did not develop either condition. This indicates the need for new therapeutic strategies to reduce HCL-treatment-associated toxicities.

scholarly journals Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Robert J. Kreitman ◽  
◽  
Claire Dearden ◽  
Pier Luigi Zinzani ◽  
Julio Delgado ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Braf Inhibitor ◽  
Nucleoside Analogs ◽  
High Rate ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Long Term Follow Up

Abstract Background Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy. Trial registration ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711

Efficacy and safety of cladribine: Subcutaneous versus intravenous administration in hairy cell leukemia.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7013-7013
Author(s):  
Tarek Yakout Mohamed ◽  
Mosaad El Gammal ◽  
Alfred Elias Namour ◽  
Raafat Ragaie Abdel Malek ◽  
Ola Khorshid
Keyword(s):  
Complete Remission ◽  
Adverse Events ◽  
Hairy Cell Leukemia ◽  
Route Of Administration ◽  
Similar Response ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Laboratory Parameters ◽  
Significant Difference

7013 Background: Hairy cell leukemia (HCL) is rare B-cell lymphoproliferative disorder. Its treatment has evolved from splenectomy with time to failure (TTF) of 19 months to Cladribine that increased complete remission (CR) rate to 90%, with only small percentage of patients relapsing at 30 months. Cladribine (CDA) is originally administered intravenously as continuous infusion for 7 days; Subsequently, it was administered subcutaneously. This study aims at comparing efficacy and toxicity of Subcutaneous (SC) versus Intravenous (IV) administration of CDA in treatment of HCL. Methods: This retrospective study included HCL patients presented to National Cancer Institute and Nasser Institute, Cairo, Egypt, during period 2004-2010. Included patients received CDA as 1st or 2nd line with minimum follow up of 12 months. All files were reviewed for baseline clinical & laboratory parameters, route of administration, response, adverse events and survival. Results: This study included 49 eligible patients, 41 patients received CDA as 1st line treatment, while 8 patients as 2nd line. Eighteen patients were treated by continuous IV infusion whereas 31 patients by SC injections. Both groups were comparable regarding baseline clinical and laboratory parameters with no statistically significant difference. At median follow up period of 33.5 months, complete remission rate was 94% in IV group versus 97% in SC group (p=0.691); median TTF for IV group was 52.9 months while that for SC group was not reached (p=0.035). The median time to achieve CR in both arms was similar. By analyzing different factors affecting TTF using multivariate analysis, route of administration proved to be the only statistically significant factor (P=0.006). Regarding adverse events, there was no difference between both groups in hematological toxicities. IV route was associated with a significant higher incidence of mucositis (p=0.02) and viral infections (p=0.01). Hepatotoxicity and neurotoxicity were higher in SC group but difference was not statistically significant. Conclusions: SC administration of cladribine is an alternative route to IV in treatment of HCL with similar response rate, longer time to treatment failure and better tolerability.

scholarly journals A Unique Hairy Cell Leukemia Variant

2016 ◽  
Vol 9 (2) ◽  
pp. 312-316
Author(s):  
Charles Jian ◽  
Cyrus C. Hsia
Keyword(s):  
Flow Cytometry ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Nucleoside Analogs ◽  
B Cell Lymphoma ◽  
Purine Nucleoside ◽  
Peripheral Blood Flow ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Normal Peripheral Blood

A 65-year-old woman presented with easy bruising, left upper quadrant pain, decreased appetite, and weight loss. She had splenomegaly and lymphocytosis (lymphocyte count of 11.6 × 109/l), with remarkably abnormal appearing morphology. Her hemoglobin and platelet counts were normal. Peripheral blood flow cytometry revealed a monoclonal B-cell population expressing CD11c, CD25, CD19, CD20, and CD103. An initial diagnosis of hairy cell leukemia (HCL) was made, and the patient was treated with a standard 5-day course of cladribine. However, her lymphocytosis improved transiently, with a relapse 4 months later. There was no improvement in her splenomegaly. An HCL variant (HCL-v) was considered based on her resistance to treatment with a purine nucleoside analog. A subsequent splenectomy improved symptoms. Two years after, the patient suffered a relapse and underwent 6 cycles of CHOP-R (cyclophosphamide, hydroxydaunomycin, oncovin, prednisone, and rituximab), achieving partial remission. While under observation, she progressed with lymphocytosis 6 months later and was treated with pentostatin. There was no significant improvement in her disease, and she died 8 weeks following treatment initiation. HCL-v is a clinically more aggressive mature B-cell lymphoma than HCL with worse splenomegaly, higher lymphocyte counts, and resistance to typical HCL therapy with purine nucleoside analogs. Early recognition of HCL-v in the history, physical examination, and investigations with morphology and flow cytometry is key to patient management. Further, as in our case of HCL-v, cell morphology can be distinctly atypical, with large nucleoli and extremely convoluted nuclei. The distinction between HCL and HCL-v is important as HCL-v patients require more aggressive therapy and closer follow-up.

Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up.

1997 ◽  
Vol 15 (3) ◽  
pp. 1138-1142 ◽  
Author(s):  
M A Hoffman ◽  
D Janson ◽  
E Rose ◽  
K R Rai
Keyword(s):  
Hairy Cell Leukemia ◽  
Opportunistic Infections ◽  
Medical Center ◽  
Second Malignancies ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Island Jewish Medical ◽  
Negative Phenotype

PURPOSE To analyze initial and long-term outcomes after treatment of patients with active hairy-cell leukemia (HCL) with a single cycle of cladribine (2-CdA). PATIENTS AND METHODS Forty-nine patients with active HCL were treated with 2-CdA by continuous intravenous infusion at 0.1 mg/kg/d for a total of 7 days at the Long Island Jewish Medical Center between September 1990 and August 1992. Here we report on all patients followed-up until April 1996. RESULTS At 3 months after treatment, complete response (CR) occurred in 37 patients (76%) and partial response (PR) occurred in 12 patients (24%), for an overall response rate of 100% (95% confidence interval, 94% to 100%). At a median follow-up of 55 months, the relapse-free survival is 80% and overall survival is 95%. Ten patients (20%) have relapsed. Of the 26 patients in whom lymphocyte phenotyping was performed, four were found to have a CD25-negative phenotype. All four of these patients had PRs only and all relapsed. Eight patients have been re-treated with 2-CdA, and all achieved at least a partial remission; two of these have already relapsed with remission durations of less than 1 year. Five second malignancies have occurred in four patients. CONCLUSION With a median follow-up of more than 4 years, 39 patients (80%) continue in remission. Only two deaths have occurred. A CD25-negative phenotype may predict for a poorer response to 2-CdA. Patients who relapse may be re-treated with 2-CdA, but subsequent remissions may be of shorter duration. There has not been a markedly increased incidence of second malignancies or late opportunistic infections.

scholarly journals Adverse Events Among Patients with Hairy Cell Leukemia Treated with Purine Nucleoside Analogs in the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4833-4833
Author(s):  
Narendranath Epperla ◽  
Melissa Pavilack ◽  
Temitope O Olufade ◽  
Richa Bashyal ◽  
Jieni Li ◽  
...  
Keyword(s):  
Index Date ◽  
Opportunistic Infections ◽  
Nucleoside Analogs ◽  
Baseline Period ◽  
Infectious Complications ◽  
Prevalence Rates ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Number Of Patients

Abstract Introduction: Purine nucleoside analogs (PNAs) are the recommended first-line treatment in patients with hairy cell leukemia (HCL) owing to their efficacy. However, because of the rarity of this disease, little is known about clinically significant adverse events (AEs) outside of previously performed clinical trials. This retrospective claims-based study of patients treated in the current era of improved supportive care assessed the incidence and prevalence rates of AEs associated with PNA use and healthcare resource utilization (HRU) among patients with HCL enrolled in the Truven MarketScan Commercial Claims and Encounters and the Medicare Supplemental databases. Methods: Adults (≥18 years old) diagnosed with HCL (≥2 medical claims ≥30 days apart) between January 1, 2006 and December 31, 2015 were included in the study. All patients had ≥1 claim for PNA therapy (cladribine or pentostatin ± rituximab) after the HCL diagnosis date and the 1st prescription claim was defined as the index date. Continuous health plan enrollment for ≥6 months pre- (baseline period) and ≥12 months post-index date (follow-up period) was required. Patients treated with a PNA during the baseline period were excluded. Incidence rate was defined as the number of new cases of an AE during the follow-up period divided by the number of patients at risk (patients without any evidence of the adverse event in the 6-month baseline period). Prevalence rate was defined as the number of all AEs (existing cases during the baseline period and new cases during the follow-up period) divided by the total number of patients. Incidence and prevalence rates were calculated as rate per 1000 patient-years at risk. To evaluate the HRU, PNA-treated patients with HCL were categorized based on occurrence of highest AE during the follow-up period. Generalized linear model (GLM) compared HRU during the 12-month follow-up, adjusting for demographic, clinical characteristics, and baseline total healthcare costs. Results: In total, 647 PNA-treated patients with HCL were identified. Mean age (standard deviation) was 57.1 (12.2) years. Most patients were men (81.5%) and resided in the southern USA (32.2%). Over the 12-month follow-up period, 87.2% of the PNA-treated patients developed at least one AE. PNA-related AEs with the highest incidence rate were myelosuppression, anemia, and skin toxicities. The prevalence rate showed a similar trend for PNA-related AEs. Infectious complications including opportunistic infections were seen at a high rate (Table 1). The incidence and prevalence of infectious complications overall were 23.5% and 39.3% (235 and 393 per 1000 patient-years), respectively. Patients who developed myelosuppression had a higher rate of hospitalization compared with those who did not (47.4% vs 12.2%; p<0.0001) and had a longer inpatient length of stay (LOS) (3.4 vs 0.8 [days]; p=0.001). A higher proportion of patients who developed opportunistic infections were hospitalized compared with those who did not (53.7% vs 30.8%; p=0.025) and had a longer inpatient LOS (5.4 vs 2.4 [days]), although this was not statistically significant (p=0.138). Conclusion: This large claims-based dataset of patients with HCL treated with PNAs shows that a substantial proportion of patients developed AEs, including myelosuppression (most frequent) and infectious complications. Because of the nature of the data set, information regarding mortality is not currently available. However, infections due to myelo- and immunosuppression are known to be the most frequent causes of death in this patient population. These findings indicate a need for larger studies evaluating the outcomes of patients with HCL treated with approved therapies to understand better their short- and long-term toxicities, as well as for the development of therapies with lower risks of myelo- and immunosuppression. Disclosures Pavilack: AstraZeneca: Employment. Olufade:AstraZeneca: Equity Ownership; AstraZeneca: Employment. Bashyal:STATinMED: Employment. Li:STATinMED: Employment. Andritsos:HCLF: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy.

Long Term Follow-Up of Patients with Hairy Cell Leukemia (HCL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3473-3473 ◽  
Author(s):  
Farhad Ravandi-Kashani ◽  
Hagop Kantarjian ◽  
Stefan Faderl ◽  
Susan O’Brien ◽  
Deborah Thomas ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Nucleoside Analogs ◽  
Time Of Death ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Long Term Follow Up

Interferon-a (IFN-a) and, more recently, nucleoside analogs (NA) such as 2-CDA and pentostatin have been used with significant success to treat HCL. A single course of 2-CDA produces response rates over 75%, with responses maintained for 4 years in 75% of pts. Similar results have been observed with pentostatin. (Dearden et al, Br J Haematol1999;106:515). To learn more about long-term outcome, we reviewed 234 pts with untreated HCL seen at the MDACC over a 30-year period; their median follow-up was 122 months from diagnosis (up to 387 months). Their median age at diagnosis was 50 years (range 23–83 years). Survival was superior among the 173 pts given either 2-CDA (n = 161) or pentostatin (n = 12) compared to those never given either NA (p = 0.042). Figure Figure Relapse occurred in 32 of 176 pts who received 2-CDA as their first chemotherapy either at MDACC or before presenting to MDACC. Therapy for relapse after 2-CDA included rituximab (N=9), a second course of 2-CDA (n=9), a second course of 2-CDA followed by rituximab (n=8), and other (n=6). No statistically significant differences in survival were seen possibly due to small pt numbers. The estimated 10-year and 20-year survival (from diagnosis) for the 176 pts who received 2-CDA as first chemotherapy was 84%, and 65%, respectively. Figure Figure The majority of pts who died were not in remission at time of death and thus presumably died of HCL. Hence alternatives to NA are needed in at least some pts, and we are evaluating whether covariates exist that might distinguish pts who do and do not relapse and, among the former, pts whose remissions are short. Pending identification of the latter and keeping in mind the length of the average remission, alternatives to NA should have very little toxicity. We have begun to add rituximab to 2-CDA to lengthen remission duration and thus extend survival in pts with untreated HCL.

scholarly journals A single cycle of 2-chlorodeoxyadenosine results in complete remission in the majority of patients with hairy cell leukemia

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2203-2209 ◽  
Author(s):  
MS Tallman ◽  
D Hakimian ◽  
D Variakojis ◽  
D Koslow ◽  
GA Sisney ◽  
...  
Keyword(s):  
Complete Remission ◽  
Interferon Alpha ◽  
Hairy Cell Leukemia ◽  
Complete Recovery ◽  
Community Acquired Pneumonia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Single Cycle ◽  
Severe Pancytopenia

Abstract Twenty-six patients with hairy cell leukemia (HCL) were treated with 2- chlorodeoxyadenosine (2-CdA), a purine analogue resistant to adenosine deaminase, at 0.1 mg/kg/d for 7 days by continuous intravenous infusion. Fifteen patients were previously untreated, while 11 patients had received prior treatment with splenectomy alone (three patients), interferon alpha alone (four), splenectomy, then interferon alpha (two), or splenectomy, interferon alpha, then 2-deoxycoformycin (2-DCF) (two). Sixteen (80%) of 20 patients evaluable at 3 months achieved complete remission (CR), and four (20%) achieved partial remission (PR) following a single cycle of therapy. All four patients in PR had complete recovery of their peripheral blood counts (except one patient whose platelet count remained 84,000/microL), but had residual HCL in the bone marrow (three patients) or residual splenomegaly (one). Patients with bulky adenopathy, massive splenomegaly, and severe pancytopenia responded as well as those with only modest marrow involvement. The three patients with residual marrow disease received a second cycle of 2-CdA, and two have attained CR. Therefore, 18 of 20 (90%) achieved CR with either one or two cycles of therapy. No patient achieving CR has relapsed at a median follow-up of 12 (+/- 2.1) months. Toxicities included myelosuppression and culture-negative fever. A community-acquired pneumonia was the only infectious complication. Since a single cycle of 2-CdA induces sustained CR in the vast majority of patients with minimal toxicity, this agent is emerging as the treatment of choice for all patients with HCL.

Sign in / Sign up

Export Citation Format

Share Document