Tumor flare reaction associated with lenalidomide treatment in patients with chronic lymphocytic leukemia predicts clinical response

Cancer ◽  
2010 ◽  
Vol 117 (10) ◽  
pp. 2127-2135 ◽  
Author(s):  
Asher Chanan-Khan ◽  
Kena C. Miller ◽  
David Lawrence ◽  
Swaminathan Padmanabhan ◽  
Austin Miller ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Response ◽  
Lymphocytic Leukemia ◽  
Flare Reaction

Tumor Lysis Syndrome/Tumor Flare Reaction in Lenalidomide-Treated Chronic Lymphocytic Leukemia

2007 ◽  
Vol 25 (31) ◽  
pp. 5047-5047 ◽  
Author(s):  
Laure A. Moutouh-de Parseval ◽  
Lilia Weiss ◽  
Robert J. DeLap ◽  
Robert D. Knight ◽  
Jerome B. Zeldis
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tumor Lysis Syndrome ◽  
Lymphocytic Leukemia ◽  
Tumor Lysis ◽  
Flare Reaction

Prognostic Impact of the MRD Status After Induction Treatment with Rituximab Plus Fludarabine, Cyclophosphamide and Mitoxantrone (R-FCM) in Patients with Chronic Lymphocytic Leukemia Receiving Rituximab Maintenance Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3930-3930
Author(s):  
Pau Abrisqueta ◽  
Neus Villamor ◽  
María José Terol ◽  
Eva González-Barca ◽  
Marcos González ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Maintenance Therapy ◽  
Clinical Response ◽  
Induction Therapy ◽  
Maintenance Treatment ◽  
Lymphocytic Leukemia ◽  
Induction Treatment ◽  
Prognostic Impact ◽  
Rituximab Maintenance ◽  
The Impact

Abstract Abstract 3930 Chemoimmunotherapy combination regimens achieve high rates of negative minimal residual disease responses in CLL, which has been correlated with prolonged PFS and OS. In the present study, we addressed the prognostic value of MRD levels obtained after rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) induction treatment in the response duration of patients with CLL included in the GELLC-1 trial and receiving maintenance rituximab treatment (Bosch et al. J Clin Oncol 27:4578–4584, 2009). Patients achieving CR or PR after R-FCM induction received rituximab maintenance consisting of rituximab 375 mg/m2 every three months for two years (up to 8 cycles). MRD was evaluated by four-color flow cytometry assays giving a sensitivity < 10−4 in paired peripheral blood (PB) and bone marrow (BM) samples three months after R-FCM induction therapy, every 6 months during rituximab maintenance, and at the final restaging 3 months after conclusion of treatment. Sixty-seven patients (median age 60 years, 70% male) received a median of 8 cycles of rituximab maintenance (range, 1 to 8), 76% of them completing the entire planned treatment. After R-FCM induction, MRD was considered negative in 45/59 patients (76%) in PB and in 35/63 patients (55%) in BM. Of note, these patients with negative MRD in PB had longer PFS in comparison to those with detectable MRD (at 4 years, 88%, [95%IC 98%-78%] vs 27%, [95%IC 51%-3%] respectively; p<0.01) (Figure 1). MRD negativity in BM showed a trend for a prolonged PFS (p=0.056). When MRD levels in BM after R-FCM induction where categorized, we observed that PFS was similar between the MRD negative (<10−4; n=35) and intermediate (>10−4 to <10−2; n=20) subgroups, whereas it was significantly shorter in patients showing high (>10−2, n=8) MRD levels (PFS at 4 years, 84%, 74%, and 25%, respectively, p<0.01). MRD levels after RFCM induction were compared between PB and BM paired samples. Whereas 12/57 patients (21%) that were MRD negative in PB resulted positive in BM, all patients with negative MRD in BM also had negative MRD in PB. Patients with discrepancies (negative in PB but positive in BM) in their MRD status presented a similar PFS than those with negative MRD in BM (4 year PFS, 85% vs. 90%, P=NS). The impact of MRD levels in PB achieved after R-FCM induction on PFS was also analyzed. MRD status proved to be a superior predictor for PFS than clinical response (Figure 2). In addition, when different prognostic variables (lymphocyte doubling time [LDT, cutoff 12 months], ZAP-70, serum ß2microglobulin and LDH, cytogenetic abnormalities, and MRD levels) were analyzed as predictors for PFS, only MRD status in PB along with LDT remained significantly predictive. After rituximab maintenance, 40.6% of patients achieved a MRD-negative CR, 40.6% a MRD+ CR, 5% a PR, and 14% failed to treatment. Median time to conversion from negative to positive MRD was 45.4 months, significantly longer than that observed in patients treated with FCM only (45.4 vs. 16.4 months; p=0.011) (Bosch et al. Clin Can Res 14:155–161,2008). Moreover, 3 patients that achieved MRD negative in PB but remained MRD positive in BM after the initial R-FCM treatment, became MRD-negative in BM upon rituximab maintenance. Patients that remained MRD negative in PB at the end of rituximab maintenance treatment had an excellent outcome with a PFS of 93% at 4 years in comparison to 68% in patients with MRD positive status (p=0.016). In conclusion, in patients receiving rituximab maintenance MRD levels obtained after R-FCM induction correlated with PFS duration, this correlation being independent of the clinical response attained. The sensitivity of the detection of MRD in these patients was higher in BM than in PB. Finally, maintenance treatment with rituximab seems to prolong the PFS of patients with MRD positive status, minimizing the negative impact of low levels of MRD after induction therapy. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures: Off Label Use: Rituximab is currently not approved as maintenance therapy for patients with chronic lymphocytic leukemia. Bosch:Hoffman La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Cereblon expression predicts clinical response in chronic lymphocytic leukemia treated with a thalidomide/fludarabine regimen

2014 ◽  
Vol 56 (3) ◽  
pp. 808-810 ◽  
Author(s):  
Krzysztof Jamroziak ◽  
Janusz Szemraj ◽  
Tadeusz Robak ◽  
Andrzej Tukiendorf ◽  
Krzysztof Giannopoulos
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Response ◽  
Lymphocytic Leukemia

scholarly journals Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 2878-2884 ◽  
Author(s):  
MJ Keating ◽  
S O'Brien ◽  
H Kantarjian ◽  
W Plunkett ◽  
E Estey ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Response ◽  
Alkylating Agents ◽  
Single Agent ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Strongly Correlated ◽  
Prior Therapy ◽  
Previously Treated

Abstract The clinical response and survival of 113 patients with at least 3-year follow-up after treatment with fludarabine as a single agent for chronic lymphocytic leukemia has been evaluated. Seventy-eight patients were previously treated and 35 were untreated. The response to therapy and survival were strongly correlated with the degree of previous therapy, the stage of disease, and whether or not the patients were refractory to alkylating agents. Other characteristics associated with survival were the age of the patient and the serum albumin level at the start of therapy. The median time to progression of responders who had not received prior therapy was 33 months and was 21 months for previously treated patients. Survival after progression of disease was also strongly correlated with the degree of prior therapy. No successful salvage regimen after initial fludarabine therapy was shown for patients refractory to alkylating agents, although fludarabine achieved further remissions in patients who had received fludarabine as their initial treatment or were not refractory to alkylating agents. The morbidity of patients in unmaintained remission on discontinuation of fludarabine was low, with less than one episode of infection per patient-year at risk. The morbidity during this time was correlated with clinical response and whether the patients had received prior therapy. Although fludarabine is a very effective cytoreductive regimen, most patients, including those who achieved true complete remissions, will have recurrent disease. Longer follow-up and comparative trials are required before the effect of fludarabine on survival is shown.

scholarly journals Relationship between in vitro drug sensitivity and clinical response of patients to treatment in chronic lymphocytic leukemia

2015 ◽  
Vol 46 (3) ◽  
pp. 1259-1267 ◽  
Author(s):  
MAŁGORZATA ROGALIŃSKA ◽  
JERZY Z. BŁOŃSKI ◽  
PAWEŁ GÓRALSKI ◽  
EWA WAWRZYNIAK ◽  
MARIUSZ HARTMAN ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Response ◽  
Drug Sensitivity ◽  
Lymphocytic Leukemia

scholarly journals Clinical response and pharmacokinetics from a phase 1 study of an active dosing schedule of flavopiridol in relapsed chronic lymphocytic leukemia

Blood ◽  
2009 ◽  
Vol 113 (12) ◽  
pp. 2637-2645 ◽  
Author(s):  
Mitch A. Phelps ◽  
Thomas S. Lin ◽  
Amy J. Johnson ◽  
Eunju Hurh ◽  
Darlene M. Rozewski ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Response ◽  
Phase 1 ◽  
Tumor Lysis Syndrome ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Parameter Estimates ◽  
Population Parameter ◽  
Time Curve ◽  
Mixed Effects Modeling

Abstract We previously reported interim results of a phase 1 trial in patients with chronic lymphocytic leukemia (CLL) whereby flavopiridol was administered intravenously as a 30-minute bolus followed by 4-hour infusion. We now report full pharmacokinetic (PK) data, correlations of PK with clinical outcomes, and final response and progression-free survival (PFS). Twenty-one (40%) of 52 patients with relapsed CLL achieved a partial response (PR) with a median PFS of 12 months. Responders included 17 (40%) of 43 fludarabine refractory patients, 7 (39%) of 18 patients with del(17p13), and 14 (74%) of 19 patients with del(11q22). Six responders received repeat therapy at relapse, and 5 responded again with a second median PFS of 10 months. Noncompartmental analysis and nonlinear mixed effects modeling was used to estimate PK parameters and evaluate covariates. Two-compartment population parameter estimates were 31.4 L/h, 65.8 L, 8.49 L/h, and 157 L for CL, V1, Q, and V2, respectively. Flavopiridol area under the plasma concentration-time curve (AUC) correlated with clinical response and cytokine release syndrome, and glucuronide metabolite AUC correlated with tumor lysis syndrome. These composite results confirm high activity of this pharmacokinetically derived schedule in relapsed, genetically high-risk CLL. Furthermore, PK describes some, but not all, variability in response and toxicity.

Ibrutinib treatment via alternative administration in a patient with chronic lymphocytic leukemia and dysphagia

2020 ◽  
pp. 107815522096744
Author(s):  
Kristyn Y DiSogra ◽  
Thuy Tran ◽  
Justin R Arnall ◽  
Amanda Janes ◽  
Donald C Moore ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Response ◽  
Lymphocyte Count ◽  
Absolute Lymphocyte Count ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Oral Dosage ◽  
Manuscript Preparation ◽  
Transfusion Independence ◽  
Alternative Method

Introduction Ibrutinib is a small molecule inhibitor of Bruton’s tyrosine kinase indicated for the treatment of a variety of B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenstrom’s macroglobulinemia. These indolent hematologic malignancies are considered diseases of the elderly, a population that may have dysphagia leading to difficulty swallowing tablets and capsules. Ibrutinib is currently not available in a liquid oral dosage form. We report the utilization and clinical outcomes associated with alternative administration of ibrutinib capsules in a patient with chronic lymphocytic leukemia and significant dysphagia. Case report An 86-year old female requiring chronic lymphocytic leukemia-directed therapy due to a rising absolute lymphocyte count and worsening, transfusion-dependent anemia with a past medical history of dementia and dysphagia, was initiated on ibrutinib. Management & outcome Due to the patient’s significant inability to swallow, ibrutinib capsules were administered via an alternative method by opening them and sprinkling onto soft food or applesauce. With ibrutinib therapy, the patient has had a significant clinical response in her chronic lymphocytic leukemia as evidenced by her decreased absolute lymphocyte count and achieving transfusion independence with improvements in hemoglobin. Discussion Ibrutinib administration via this alternative method resulted in an initial clinical response in the treatment of our patient’s chronic lymphocytic leukemia as evidenced by a decreasing absolute lymphocyte count and improved anemia that achieved transfusion independence. The patient has maintained this response to therapy after approximately 1 year at the time of manuscript preparation.

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