Cancer Treatment Today » Chronic Lymphocytic Leukemia

Rituxan for Hairy Cell Leukemia

M Levin, MD — Wed, 01 Jan 2014 18:49:22 +0000

Recent literature suggests that a subgroup of Hairy Cell Leukemia(HCL), sometimes called Variant Hairy Cell(HCL-V) may in fact be a different type of Lymphoma and not Hairy Cell, and that it may respond to rituximab to a much higher extent than common Hairy Cell does. It is what was called Leukemic Reticuloendotheliosis in the past. It accounts for approximately 0.4% of chronic lymphoid malignancies and 10% of all HCl cases. In contrast to HCl-C, HCl-V is a more aggressive disease and according to the new WHO classification it is no longer considered to be biologically related to HCl-C. Patients with HCl-V have an elevated white blood count, easy-to-aspirate bone marrow (unlike HCL) and weak reactivity to tartrate – resistant acid phosphatase (TRAP). HCl-V cells are positive for CD103 and CD11c and negative for CD25. The HCl-V cells express also the B-cell antigens, CD19, CD20 and CD22. The HCl-V patients frequently have an unmutated Ig gene configuration. Currently, the principles of therapy for this rare disease derive from uncontrolled single institutional studies, or even single case reports. In contrast to HCl-C, the HCl-V respond to purine nucleoside analogs (PNA) but response is limited to partial responses in approximately 50% of patients. However, complete responses were observed in some patients treated with rituximab and anti-CD22 immunotoxins.

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Gleevec for acute lymphocytic leukemia – pro

M Levin, MD — Sat, 01 Sep 2012 22:12:17 +0000

Lay Summary: There is now evidence that GLeevec is very effective in Philadelphia chromosome positive ALL.

Philadelphia-positive ALL is a very difficult disease to treat successfully. In the recent past, the standard approach was to use daunorubicin/vincristine/prednisone-based induction therapy to achieve remission and then, if the patient was a reasonable candidate and a donor could be found, to perform an allogeneic transplant. Now, the use of tyrosine kinase inhibitor therapy may be altering this strategy. Single-agent treatment with imatinib and probably with dasatinib is fairly likely to achieve hematologic responses, but the likelihood of cytogenetic response is lower.

A study reported by Dr. Kirk Schultz on behalf of the Children’s Oncology Group (COG) showed that imatinib mesylate could be given safely in combination with chemotherapy in children with Philadelphia-positive ALL. Patients aged 1-21 with Philadelphia-positive ALL who achieved remission with standard COG induction therapy received an intensive multidrug combination chemotherapy regimen, with introduction of imatinib at 340 mg/m2 for 21 days into an increasing number of treatment blocks in successive cohorts of patients. Patients receiving imatinib had a higher incidence of transaminase elevation in first consolidation and maintenance. However, there were few significant additional increased toxicities compared with historical and contemporaneous controls not receiving imatinib. This appeared to be a feasible combination of a targeted therapy with chemotherapy and will be explored further in subsequent trials.

Dr. Deborah Thomas, a pioneer in the use of imatinib mesylate and chemotherapy in adults with Philadelphia-positive ALL, presented her most recent data at ASH 2007. This is the Phase II Pilot Study of Intensified Chemotherapy With or Without Allogeneic Hematopoietic Stem Cell Transplantation in Children With Very High-Risk Acute Lymphoblastic Leukemia. The chemotherapy backbone was the MD Anderson standard of hyper-CVAD, which is fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and high-dose ara-C. Although a high rate of remission was achieved historically with the use of this regimen in patients with Philadelphia-positive ALL, disease-free survival was brief. Dr. Thomas and colleagues added imatinib at 400 mg per day on days 1 through 14 to each of 8 courses followed by 12 months of imatinib. In later iterations of her work, imatinib was increased to 600 mg per day on days 1 through 14 for courses 1 through 8, with imatinib being given indefinitely after maintenance was completed. Overall, 52 patients with imatinib-naive or minimally treated Philadelphia-positive ALL received therapy from April 2001 to July 2006. With a 3-year treatment follow-up, there were only 7 relapses (14%); however, 12 patients died. The 3-year remission and disease-free survival rates for the combination compared favorably with hyper-CVAD alone (83% vs 24%, and 55% vs 14%, respectively).

Schultz KR, Aledo A, Bowman WP, et al. Minimal toxicity of imatinib mesylate in combination with intensive chemotherapy for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) in children: a report of the Children’s Oncology Group (COG) AALL0031 protocol for very high risk ALL. Blood. 2006;108:87a. Abstract 283.
Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004;103:4396-4407
Oliver G. Ottmann andBarbara WassmannTreatment of Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia ASH Hematology 2005© 2005 The American Society of Hematology

Maintenance Rituxan for CLL

M Levin, MD — Mon, 13 Aug 2012 14:23:12 +0000

Rituximab has been shown to prolong survival when used therapeutically with chemotherapy in Chronic Lymphocytic Leukemia(CLL). Rituximab, the mAb targeting CD20, was approved by the US FDA for patients with relapsed low-grade non-Hodgkin lymphoma. It is counterintuitive why Rituxan works in CLL. Relatively low levels of CD20 are expressed on CLL B cells, compared to normal B or neoplastic B cells of other lymphomas. In addition, soluble CD20 has been demonstrated in plasma of patients with CLL; this would be expected to “soal up” and inhibit the capacity of rituximab to bind to CLL B cells, thereby resulting in rapid clearance and negatively affecting pharmacokinetics. Standard-dose rituximab (375 mg/m2 weekly for 4 weeks) has very limited activity for patients with CLL. Dose-intense and dose-dense single-agent rituximab has been shown to increase efficacy but remains experimental. Rituxan at standard dose is listed by NCCN as a single agent only for frail patients who cannot tolerate other treatments. A 2005 guideline (Imre et al) says: “There is currently insufficient evidence to support or refute the additional use of rituximab as a maintenance therapy in patients who have completed chemotherapy plus rituximab.” However, NCCN doest list it as a single agent for the elderly. As recently as 2005, a recent guideline (Imre et al) said: “There is currently insufficient evidence to support or refute the additional use of rituximab as a maintenance therapy in patients who have completed chemotherapy plus rituximab.”

Since this guideline, additional evidence has accrued to support rituximab for maintenance in CLL. The strongest evidence in support of it was the Primary Rituximab and Maintenance (PRIMA) Study, in which patients received immunochemotherapy. Those who did not fail were randomly assigned to maintenance or observation. There was a longer progression-free survival in those who received rituximab maintenance, but no survival benefit. There also was a study, in which patients who could be observed were either randomly assigned to the watch-and-wait approach or to rituximab induction and maintenance. Time to requiring next treatment was longer if you got rituximab, but there was no survival benefit.

Not having a survival benefit means that the disease can be pushed off form coming back by using Rituxan but this treatment will not ultimately prolong life.

Currently(2012) are no guidelines that recommend maintenance rituximab.

The drugs thalidomide and lenalidomide, have also been investigated as maintenance treatment in CLL. Lenalidomide might have some validity as maintenance treatment and clinical trials of lenalidomide in maintenance treatment have been initiated.

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