Rituximab and High-Dose Dexamethasone (R-dex) Is Effective In The Treatment Of Relapsed/Refractory Chronic Lymphocytic Leukemia

Abstract Introduction High-dose methylprednisolone (HDMP) in combination with rituximab is active in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) but serious infections are frequent. Recently published data suggest that high-dose dexamethasone might be equally effective to HDMP despite lower cumulative dose. Aims To assess efficacy and safety of high-dose dexamethasone combined with rituximab (R-dex) in relapsed/refractory CLL. Patients and Methods A total of 60 pts (pts) with relapsed/refractory CLL treated at a single tertiary center between September 2008 and October 2012 were included in this retrospective analysis. Basic characteristics are summarized in Table 1. The schedule of R-dex consisted of rituximab 500 mg/m2 i.v. day 1 (375 mg/m2 in cycle 1) and dexamethasone 40 mg orally on days 1-4 and 10-13. Treatment was repeated every 3 weeks for a maximum of 8 cycles. All pts received antimicrobial prophylaxis with sulfamethoxazole/trimethoprim and aciclovir. Results Median number of administered R-dex cycles was 6 (range, 1-8). The overall response (ORR)/complete remissions (CR) were achieved in 75/3%. At the median follow-up of 9 months, median progression-free survival was 8 months and median overall survival 24 months. Significant predictors of short PFS in univariate analysis were bulky lymphadenopathy (p=0.023) and refractoriness to fludarabine (p=0.02). Interestingly, activity of R-dex in bulky fludarabine-refractory CLL was similar to ofatumumab (ORR 62 %, median PFS, 4 months, median OS, 12 months) (Wierda et al., 2010). R-dex was successfully used as a debulking regimen before allogeneic stem cell transplantation in 8 patients. Serious (CTCAE grade III/IV) infections occurred in 29% of patients; 19% pts developed steroid diabetes requiring temporary short-acting insulin. Conclusions Our data show that R-Dex is an active and feasible treatment for patients with relapsed/refractory CLL; however, major infections remain relatively frequent despite combined antimicrobial prophylaxis. In addition, durable responses are infrequent. Therefore, further optimization of this therapeutic approach is warranted. Updated results will be presented. Disclosures: No relevant conflicts of interest to declare.

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Retrospective Review of Appropriate Use of Antimicrobials and Anticoagulants in Patients Hospitalized for a Malignant Hematologic Condition

Blood ◽

10.1182/blood-2019-121534 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2116-2116

Author(s):

Louis-Bassett Porter ◽

Hanaa Shihadeh ◽

Kim Dittus

Keyword(s):

Conflicts Of Interest ◽

Antimicrobial Prophylaxis ◽

Lymphocytic Leukemia ◽

High Dose ◽

Cell Transplant ◽

Maintenance Chemotherapy ◽

Appropriate Use ◽

Hematopoietic Stem ◽

Platelet Counts ◽

Anticoagulant Prophylaxis

Background Interventions for venous thromboembolism (VTE) prophylaxis and primary antimicrobial prophylaxis for chemotherapy-induced neutropenia and hematopoietic stem cell transplant (HSCT) recipients have resulted in reduced rates of VTE and infection. Appropriate prevention of thrombosis and infection requires a day-to-day evaluation in hospitalized hematology patients experiencing changing chemotherapy regimens and fluctuating neutrophil or platelet counts. Inappropriate use of anticoagulants in patients with thrombocytopenia may result in iatrogenic bleeding. Methods To evaluate appropriate antimicrobial and anticoagulant prophylaxis, a retrospective extraction of electronic medical records of hematology inpatients meeting eligibility criteria from 06/2017 - 06/2018 was completed. Appropriate use was determined by the University of Vermont Medical Center's internal protocols, which are derived from the current standard of care. Anti-viral prophylaxis (AVP) is required for any hospital day for patients undergoing HSCT and was within 180 days of transplant, or having a diagnosis of acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL), while on induction, consolidation, or maintenance chemotherapy, or was receiving specific therapy (e.g., Hyper-CVAD, CODOX-M, R-DA-EPOCH, VD-PACE, bendamustine, alemtuzumab (stopping when CD4 count >200), proteosome inhibitors, or Daratumumab). Anti-pneumocystis prophylaxis (APP) is required for any hospital day for patients diagnosed with ALL (on induction, consolidation, or maintenance chemotherapy, or therapies listed above), receiving high dose steroids (prednisone >20 mg/day or dexamethasone >4 mg/day for 30 or more days), purine analogs (e.g., fludarabine, clofarabine) or undergoing HSCT (after platelet engraftment). Antimicrobial prophylaxis was considered inappropriate when the above conditions were met but the patient was not provided the appropriate therapy during an inpatient day and did not have a documented contraindication. Anticoagulant prophylaxis (ACP) was considered inappropriate when an anticoagulant was provided on a hospital day when platelets were less than 50 K/cmm. Days where the patient missed a dose at admission or discharge were excluded. Results We evaluated a total of 221 patient visit records comprised of 142 unique patients. In total, on 189 (10.9%) of 1,734 total inpatient days evaluated, appropriate antimicrobial prophylaxis was not provided (Table 1). Regarding AVP, 15 (6.8%) patients missed at least one day, a total of 69 (4.0%) days. 11 (5.0%) patients missed at least one day of APP, a total of 120 (6.9%) days. Regarding ACP, there are 1,961 platelet count observations which included 219 visits from 140 unique patients (Table 2). Of these observations, 603 (30.8%) had platelet counts below 50 K/cmm. ACP was not held 18 times (3.0%) when platelet levels fell below 50 K/cmm. 51 patients (36.4%) had their platelets drop below 50 K/cmm at some point during their visit(s) of which 7 (13.7%) did not have ACP withheld. Conclusions and Discussion The results identify areas of improvement regarding antimicrobial prophylaxis. Antimicrobial prophylaxis is often not systematically evaluated on inpatient services and as such may not be consistently evaluated by clinicians rotating on the hematology service. Conversely, guidelines for withholding anticoagulant prophylaxis were more closely followed. This is likely due to the focus in recent years on anticoagulation prophylaxis and the near universal knowledge of bleeding risk when provided at low platelet levels. Inappropriate antithrombotic prophylaxis was most frequently noted at platelets of just below 50 K/cmm (i.e., 47-49 K/cmm) and immediately discontinued for following doses as platelet values declined. A potential intervention is the use of a daily checklist that can evaluate the use of these therapies. Disclosures No relevant conflicts of interest to declare.

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Early Autologous Stem Cell Transplantation (SCT) in Genetically Poor-Risk Chronic Lymphocytic Leukemia Is Feasible and Effective: Results from a Prospective Multicenter Study (GCLLSG CLL3 Protocol).

Blood ◽

10.1182/blood.v104.11.146.146 ◽

2004 ◽

Vol 104 (11) ◽

pp. 146-146 ◽

Cited By ~ 7

Author(s):

Peter Dreger ◽

Raimonde Busch ◽

Stephan Stilgenbauer ◽

Hildegard Greinix ◽

Manfred Hensel ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Single Case ◽

Progression Free Survival ◽

Multicenter Trial ◽

Lymphocytic Leukemia ◽

Hematological Toxicity ◽

High Dose ◽

Post Transplant ◽

Poor Risk ◽

One Year

Abstract From July 1997 through June 2002, the German CLL Study Group conducted a prospective multicenter trial to assess the feasibility and efficacy of early SCT in patients with poor-risk chronic lymphocytic leukemia (CLL). The protocol comprised optional cytoreduction with CHOP, fludarabine, or FC; PBSC mobilization using the Dexa-BEAM regimen; and myeloablative therapy with TBI/CY followed by reinfusion of purged stem cells. Inclusion criteria were age <61 years, stage Binet B/C or poor-risk stage A as defined by short lymphocyte doubling time plus elevated STK, and one line of pretreatment or less. Endpoints were feasibility (as defined by the proportion of patients able to successfully undergo all study procedures); toxicity; efficacy; and quality of life (QOL) as defined by the Spitzer QOL Index. Results: As of July 2004, 128 of 179 eligible patients were evaluable. Median age was 51 (27–60) years. Binet stages were poor-risk A 15%; B 61%; C 24%. An unmutated VH rearrangement was present in 72%. Eighty-six percent of the patients were chemotherapy naive at study entry. Best documented response during the pretransplant phase was complete remission (CR) in 28% and partial remission (PR) in 64% of the patients, giving an overall response rate of 92%. Immunomagnetically purged grafts were obtained in 83% of the patients in whom mobilization was attempted, containing 4.6 (1.2–22.1) CD34+ cells per kg body weight. Altogether, 98 of 128 patients (77%) proceeded to SCT. Reasons for exclusion from SCT were disease progression, mobilization failure, toxicity during the mobilization phase, or patient’s refusal. At 3 months post SCT CR was reported in 78% and PR in 21%. With a follow-up time of 36 (3–77) months, median progression-free survival of all 128 patients intended to treat was 59 months (54 months for those with unmutated VH). 4-year overall survival of all 128 patients was 84% (95%CI 74–94). Grade 3/4 non-hematological toxicity was mainly due to infections, which occurred in 21% of the patients (18% pretransplant; 7% post transplant). Six complications were fatal (4 pretransplant, 2 post transplant), translating into a 5% probability of treatment-related death. A single case of treatment-related myelodysplasia / AML has been reported to date. One year after SCT, QOL index had the maximum score of 10 points in 48 of 57 evaluable patients (84%). In comparison to prestudy levels, QOL had increased in 35%, remained similar in 50%, and decreased in 15% of the patients. Conclusions: Early sequential high-dose therapy including SCT for poor-risk CLL is feasible and has promising efficacy. Whereas the transplant-related toxicity appears to be acceptable, future studies should aim at replacing Dexa-BEAM by a similarly effective but less toxic mobilization regimen.

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Dexamethasone, Cytarabine and Cisplatin or Oxaliplatin Schedule (DHAP or Ox-DHA) Is Effective and Widely Applicable in Chronic Lymphocytic Leukemia and Waldenström Macroglobulinemia.

Blood ◽

10.1182/blood.v114.22.3434.3434 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3434-3434

Author(s):

Marco Ruella ◽

Irene Ricca ◽

Angela Gueli ◽

Daniela Gottardi ◽

Daniele Caracciolo ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Partial Remission ◽

Conflicts Of Interest ◽

Lymphocytic Leukemia ◽

Hematological Toxicity ◽

High Dose ◽

Main Concern ◽

Low Grade ◽

First Line ◽

Salvage Regimen

Abstract Abstract 3434 Poster Board III-322 Introduction Fludarabine alone or in combination is considered the standard treatment for Chronic Lymphocytic Leukemia (CLL). A high response rate is usually observed following fludarabine, particularly if delivered together with rituximab. In spite of the high therapeutic efficacy, most patients subsequently relapse. For these patients there are no defined salvage treatments. Moreover, fludarabine-containing regimens may have some restrictions due to non-negligible side effects. In particular, there are some concerns in employing fludarabine first-line in patients with autoimmune hemolytic anemia (AHA) or with renal function impairment. In addition, fludarabine has been reported to compromise the capacity of progenitor cell mobilization. Thus, novel effective treatment approaches are needed, for the management of patients failing after fludarabine-based regimens and for those unfit to receive fludarabine first-line. A very effective salvage regimen for refractory/relapsed lymphoproliferative disorders is the DHAP combination. DHAP has been widely used in the rescue of both low-grade and high-grade lymphoma. However, its efficacy in CLL has not been verified yet. The main concern with DHAP is the well known renal toxicity of cisplatin. However, the use of the less toxic analog Oxaliplatin, might circumvent this problem. Indeed, recent reports have shown that the inclusion of oxaliplatin into the original DHAP regimen (Ox-DHA) markedly improves the tolerability and widens regimen applicability. Aim: To evaluate retrospectively feasibility and efficacy of the DHAP and Ox-DHA regimens in CLL and in other non-follicular low-grade lymphomas, in particular in Waldenström Macroglobulinemia (WM). Patients and Methods Between 2002 and 2008, 84 low-grade lymphoma patients received DHAP or Ox-DHA; their median age was 60 yrs. (range: 24-84), 58 were male; 70 patients had CLL with advanced stage (65 patients with Binet stage B and C) and 14 had WM. Thirty-eight patients were treated at first relapse, 27 at second or subsequent relapse, whereas 19 received the DHAP or Ox-DHA schedule as first-line treatment, in place of Fludarabine, due to: i. AHA (3 patients), ii. concomitant second malignancy (4 cases), iii. need of initial debulking, before a high-dose program with autograft. The original DHAP schedule requires hospitalization for three to five days; it includes: Cisplatin 100 mg/sqm on day 1, Cytarabine 2 g/sqm/b.i.d. every 12 hrs. on day 2, Dexamethasone 40 mg days 1-4. Ox-DHA can be delivered in the outpatient setting, compared to DHAP, there are two main modifications: Oxaliplatin 100 mg/sqm in two-hr i.v. infusion on day 1, and Cytarabine 2 g/sqm two doses delivered in two consecutive days (day 2 and day 3). Rituximab (375 mg/sqm) was added in 12 DHAP and 28 Ox-DHA courses. Patients aged over 70 yrs had variable dose reductions (25% to 50%). Results Ox-DHA had hematological toxicity analogous to that commonly observed with the original DHAP schedule; 11 patients required short hospitalization for severe infectious complications; 7 patients developed fever of unknown origin, 4 showed reversible peripheral neurotoxicity. The program was discontinued in four patients due to disease progression (3 patients) and AHA (1 case). There were no severe liver or renal toxicities. No toxic deaths were recorded. The overall response (OR) rate was 90%; in details, complete remission (CR), or very good partial remission (VGPR), was achieved in 41% of patients receiving DHAP without rituximab and 50% of those receiving DHAP supplemented with rituximab. In the Ox-DHA group, 50% of patients treated without rituximab and 75% of those treated with rituximab reached CR or VGPR. Among patients treated at diagnosis, overall 47% reached CR or VGPR and 42% reached partial remission (PR). The OR rate was unexpectedly high at 91% in patients treated for refractory/relapsed disease, with 66% of them achieving CR/VGPR (74% and 55% for patients at 1st and ≥ 2nd relapse, respectively) and 35% PR. Among 14 WM patients, 1 obtained a CR, 5 a VGPR, 6 a PR and 2 had a stable disease. Conclusions Dexamethasone, Cytarabine and Cisplatin or Oxaliplatin schedule is a well tolerated regimen, highly effective both front-line and in the rescue for relapsed/refractory disease in CLL and WM patients. Future clinical trials will define the real efficacy of the DHAP or Ox-DHA regimen in the management of CLL and WM patients. Disclosures No relevant conflicts of interest to declare.

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BIRC3 disruption and Copy Number Aberrations in Chronic Lymphocytic Leukemia (CLL) Patients with 11q Deletion

Blood ◽

10.1182/blood.v124.21.3295.3295 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3295-3295

Author(s):

Ilaria Del Giudice ◽

Silvia Bonina ◽

Marilisa Marinelli ◽

Luciana Cafforio ◽

Sara Raponi ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Copy Number ◽

Poor Prognosis ◽

Conflicts Of Interest ◽

Progression Free Survival ◽

Chromosome Analysis ◽

Lymphocytic Leukemia ◽

The Other ◽

11Q Deletion

Abstract Introduction. Chronic lymphocytic leukemia (CLL) with 11q deletion has been associated to a poor prognosis, but the clinical course of patients carrying this lesion is variable. This aberration, most often monoallelic, is present in 10-17% of newly diagnosed CLL and in 20-30% of patients with progressive or chemorefractory disease. The minimal deleted region (MDR) (2-3 Mbp) is located on the 11q22.3-q23.1 region and includes ATM. Moreover, 30-40% of 11q- CLL have also an inactivating ATM mutation on the other allele. The deleted region on 11q can also include BIRC3, a gene that is often deleted or mutated in advanced/chemorefractory stages of the disease. Although BIRC3 disruption has been associated to a poor prognosis, its prognostic implications in addition to ATM deletion are not well defined. The aim of this study was to perform a copy number aberration (CNA) and gene sequencing analyses on a cohort of CLL patients with 11q- in order to identify subgroups with potential prognostic relevance based on: i) the inclusion of BIRC3 in the deleted region; ii) the presence of BIRC3 mutation; iii) the presence of other CNAs. Methods. The study has included 55 untreated CLL patients followed at our Institution or enrolled in GIMEMA clinical trials (2003-2013). Genomic DNA was extracted from peripheral blood samples. CNA analysis was performed by genomic hybridization on the CytoScan HD array (Affymetrix), which contains more than 2.6 x 106 markers for copy number analysis and 750.000 SNPs. Data were analyzed using both Partek Genomics Suite and ChAS (Chromosome Analysis Suite, Affymetrix) software. The resulting CNAs were verified by visual examination of the plotted copy number profiles. BIRC3 mutations (exons 6-9) were evaluated by Sanger sequencing. Time to first treatment (TFT) was calculated from the date of diagnosis to the date of first therapy or last follow-up; progression-free survival (PFS) from the date of first therapy to the date of progression, death or last follow-up. Results. Baseline characteristics of the 55 cases were as follows: median age at diagnosis 59 years (range 39-84), male gender in 81.8% of patients, progressive disease in 62%. All patients showed 11q- by FISH (median 80%, range 25-99% of nuclei); germline IGHV were present in 96.4% of cases; TP53 deletion in 1 case and TP53 mutation in none; NOTCH1 mutation in 4/40 cases; SF3B1 mutation in 5/40 (all mutually exclusive with only 1 case having both SF3B1 and BIRC3 mutations). By CytoScan HD array, the size of 11q- was very variable, ranging from 0.36 Mbp to 65.14 Mbp; the MDR was located on 11q22.3 region, encompassing 4 genes (ACAT1, ATM, CUL5, NPAT). BIRC3 was included in the deleted region in 45/55 cases (81.8%) and was mutated in 4/54 (7.5%), being always deleted on the other allele. Beside 11q-, 51 cases (92.7%) showed several additional CNAs (average 4.9, range 1-14 per patient), with 5 recurrent lesions: 2p gain in 11 cases, del4(p15.2) in 6, del19(p13.3) in 6, 8q gain in 5 and del4(q22.1) in 4. BIRC3 deletion was not associated to the number of additional CNAs nor to specific CNA. After a follow-up of 59.6 months (range 7.4-229.7), 40 of 47 evaluable patients have received treatment (median TFT 15.8 months, range 0-167). BIRC3 deleted cases (n=37) showed a TFT not significantly different from WT cases (n=10). Conversely, BIRC3 mutation was associated to a shorter TFT (p <0.0001), 0.5 vs 19.3 months of WT cases. Notably, 3/4 cases with the biallelic BIRC3 disruption had a marked hyperleukocytosis at diagnosis (212.4-302.8 x 109L). The presence of additional CNAs was associated to a shorter, though not significant, TFT considering either >3 CNAs larger than 5 Mb (n=14) or >10 CNAs (n=5), or the presence of 2p gain, del4(p15.2), del19(p13.3) or 8q gain. So far, 22 patients have been evaluated for PFS after first-line therapy (median 28.7 months). BIRC3 deleted cases (n=17) were not associated to a shorter PFS compared to WT cases (n=5), in line with the results from Rose-Zerilli et al (Haematologica 2014). Conclusions. Among CLL with 11q-: 1) BIRC3 deletion involves more than 80% of cases, whilst the mutation is rare (7.5%); 2) BIRC3 deletion is not associated to a higher genomic complexity; 3) BIRC3 deletion does not seem to influence TFT or PFS of 11q- CLL; 4) BIRC3 mutation is strongly associated to a short TFT; 5) BIRC3 biallelic lesions can be associated to a marked hyperleucocytosis at diagnosis and immediate need of treatment. Disclosures No relevant conflicts of interest to declare.

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Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic leukemia

Leukemia & Lymphoma ◽

10.3109/10428194.2014.893306 ◽

2014 ◽

Vol 55 (12) ◽

pp. 2769-2777 ◽

Cited By ~ 5

Author(s):

Stephen P. Mulligan ◽

Karin Karlsson ◽

Mats Strömberg ◽

Viggo Jønsson ◽

Devinder Gill ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Progression Free Survival ◽

Lymphocytic Leukemia ◽

High Dose ◽

Free Survival

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Rituximab In Combination with High-Dose Dexamethasone: An Effective Treatment Option for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v116.21.4629.4629 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4629-4629

Author(s):

Michael Doubek ◽

Martin Simkovic ◽

Anna Panovska ◽

Monika Hrudkova ◽

David Belada ◽

...

Keyword(s):

Effective Treatment ◽

Treatment Option ◽

Progression Free Survival ◽

Median Number ◽

Infectious Complications ◽

Lymphocytic Leukemia ◽

High Dose ◽

Significant Activity ◽

Effective Treatment Option ◽

High Dose Dexamethasone

Abstract Abstract 4629 Background: Patients with refractory CLL have poor outcome despite currently used salvage treatment. Regimens based on high-dose corticosteroids seem to offer a promising treatment option in this scenario. High-dose methylprenisolone combined with rituximab (R-HDMP) demonstrated significant activity in relapsed/refractory CLL but serious infectious complications occurred in a substantial proportion of patients. Pilot data have shown that combination of dexamethasone and rituximab (R-Dex) may provide comparable results with less toxicity. Aims and Methods: We performed a retrospective analysis of the efficacy and safety of R-Dex in patients (pts) with CLL treated at two tertiary centers between April 2006 and February 2010. Patients received two versions of R-Dex regimen: the dose of rituximab was either 500 mg/m2 on day 1, 8, 15, 22 (375 mg/m2 in 1st cycle), repeated every 4 weeks (n=25) or 500 mg/m2 on day 1 (375 mg/m2 in 1st cycle) repeated every 3 weeks (n=16). The dose of dexamethasone was identical in both regimens: 320 mg per cycle (40 mg on day 1–4 and 10–13 or 15–18). Results: R-Dex was administered to 41 patients (19 males) with median age of 68 years (range, 44–81) indicated for treatment according to NCI-WG criteria. Autoimmune hemolytic anemia or thrombocytopenia was the only indication for the treatment in 7 patients. Rai stage III/IV was present in 37/41 pts. IgVH genes were unmutated in 24/29 pts with available results. Cytogenetic aberrations detected by FISH (n=33) revealed del 17p in 7 patients; del 11q in 11 patients; del 13q in 15 patients and trisomy 12 in 5 patients. Median number of previous therapies was 2 (0-8); 29/41 pts were previously treated with fludarabine-based regimens. The effect of R-Dex in evaluable patients without hemolysis (n=32) was: overall response rate (ORR), n= 21 (62%), complete remission (CR), n=6 (18%), partial remission (PR), n=15 (44%), stable disease (SD), n=4 (12%) and progressive disease (PD), n=5 (15%). All patients treated with R-Dex for autoimmune cytopenia achieved complete resolution of hemolysis. Grade III or IV toxicity included infections in 13 patients (32%), steroid diabetes in 6 patients (15%) and rituximab infusion-related side effects in 3 patients (7%). At the time of analysis (February 2010), median progression free survival (PFS) was 9 months; median overall survival has not been reached. There was no difference in ORR, PFS or OS between the two versions of R-Dex regimen. Conclusions: This pilot study shows that R-Dex is a feasible and effective treatment for relapsed/refractory CLL. In particular, R-Dex appears to be highly effective in CLL with autoimmune cytopenias. However, infectious toxicity remains a serious issue. In addition, long-term disease control can be expected in minority of patients only. Interestingly, higher dose of rituximab per cycle did not result in improved efficacy. Supported by research project MZO 00179906 from Ministry of Health, Czech Republic, by research grant MSM 0021620808 and by the Czech Leukemia Study Group for Life. Disclosures: Smolej: Roche: Honoraria; Bayer-Schering: Honoraria; Genzyme: Honoraria.

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Long-Term Outcomes From a Randomized Dose Optimization Study of Chimeric Antigen Receptor Modified T Cells in Relapsed Chronic Lymphocytic Leukemia

Journal of Clinical Oncology ◽

10.1200/jco.19.03237 ◽

2020 ◽

Vol 38 (25) ◽

pp. 2862-2871 ◽

Cited By ~ 5

Author(s):

Noelle V. Frey ◽

Saar Gill ◽

Elizabeth O. Hexner ◽

Stephen Schuster ◽

Sunita Nasta ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Chimeric Antigen Receptor ◽

Antigen Receptor ◽

Progression Free Survival ◽

Lymphocytic Leukemia ◽

High Dose ◽

Long Term Outcomes ◽

Free Survival ◽

Significant Difference

PURPOSE To describe long-term outcomes of anti-CD19 chimeric antigen receptor T (CART) cells in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). METHODS Between January 2013 and June 2016, 42 patients with relapsed or refractory CLL were enrolled in this study and 38 were infused with anti-CD19 CART cells (CART-19). Of these, 28 patients were initially randomly assigned to receive a low (5 × 107) or high (5 × 108) dose of CART-19, and 24 were evaluable for response assessment. After an interim analysis, 10 additional patients received the selected (high) dose and of these, eight were evaluable for response. Patients were followed for a median 31.5 months (range, 2 to 75 months). RESULTS At 4 weeks, the complete and overall responses for the 32 evaluable patients were 28% (90% CI, 16% to 44%) and 44% (90% CI, 29% to 60%), respectively. The median overall survival (OS) for all patients was 64 months; there was no statistically significant difference between low- and high-dose groups ( P = .84). Regardless of dose, prolonged survival was observed in patients who achieved a CR versus those who did not ( P = .035), with median OS not reached in patients with CR versus 64 months in those without CR. The median progression-free survival was 40.2 months in patients with CR and 1 month in those without a CR ( P < .0001). Toxicity was comparable in both dose groups. CONCLUSION In patients with advanced CLL, a 5 × 108 dose of CART-19 may be more effective than 5 × 107 CART-19 at inducing CR without excessive toxicity. Attainment of a CR after CART-19 infusion, regardless of cell dose, is associated with longer OS and progression-free survival in patients with relapsed CLL.

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Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia

Medicina ◽

10.3390/medicina55110719 ◽

2019 ◽

Vol 55 (11) ◽

pp. 719

Author(s):

Pileckyte ◽

Valceckiene ◽

Stoskus ◽

Matuzeviciene ◽

Sejoniene ◽

...

Keyword(s):

High Risk ◽

Chronic Lymphocytic Leukemia ◽

Progression Free Survival ◽

Lymphocytic Leukemia ◽

High Dose ◽

Meaningful Improvement ◽

Free Survival ◽

High Dose Methylprednisolone ◽

Unfit Patients

Background and Objectives: BTK and BCL2 inhibitors have changed the treatment paradigms of high-risk and elderly patients with chronic lymphocytic leukemia (CLL), but their long-term efficacy and toxicity are still unknown and the costs are considerable. Our previous data showed that Rituximab (Rtx) and high-dose methylprednisolone (HDMP) can be an effective and safe treatment option for relapsed high-risk CLL patients. Materials and Methods: We explored the efficacy and safety of a higher Rtx dose in combination with a shorter (3-day) schedule of HDMP in relapsed elderly or unfit CLL patients. Results: Twenty-five patients were included in the phase-two, single-arm trial. The median progression free survival (PFS) was 11 months (range 10–12). Median OS was 68 (range 47–89) months. Adverse events (AE) were mainly grade I–II° (77%) and no deaths occurred during the treatment period. Conclusions: 3-day HDMP and Rtx was associated with clinically meaningful improvement in most patients. The median PFS in 3-day and 5-day HDMP studies was similar and the toxicity of the 3-day HDMP schedule proved to be lower. The HDMP and Rtx combination can still be applied in some relapsed high-risk and elderly or unfit CLL patients if new targeted therapies are contraindicated or unavailable. (ClinicalTrials.gov identifier: NCT01576588).

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