Cancer Treatment Today » Non-Hodgkin’s Lymphoma

Rituxan or Rituxan with cladribine for Variant Hairy Cell Leukemia – pro

M Levin, MD — Fri, 18 Oct 2013 14:01:45 +0000

Recent literature suggests that a subgroup of Hairy Cell Leukemia(NCL), sometimes called Variant Hairy Cell Leukemia(HCL-V)l my in fact be a different disease not related to HCL at all and which my respond to rituximab to a much higher extent than common Hairy Cell does. It is thought that this variant is what used to be called Leukemic Reticuloendotheliosis in the past. It is an uncommon disorder accounting 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 which is difficult to aspirate, and weak reactivity to tartrate – resistant acid phosphatase (TRAP). Immunophenotypically, 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 have frequently 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 response to purine nucleoside analogs (PNA) is limited to partial responses in approximately 50% of patients. However, complete responses were observed in patients treated with rituximab and anti-CD22 immunotoxins.

For non-variant type, the use fo the first two together is based on a study reported very recently in ASCO on 3/2020 byKreitmen et al as reported in ASCO 2020. This regimen is for patients who have minimal residual disease after 6 months. In the trial, 68 patients with purine analog-naive classic hairy cell leukemia were randomly assigned to receive 0.15 mg/kg of cladribine intravenously on days 1 to 5 with eight weekly doses of rituximab at 375 mg/m2 started on day 1 (concurrent group, n = 34) or 6 months later after detection of minimal residual disease in their blood (delayed group, n = 34). Minimal residual disease tests included blood and bone marrow flow cytometry and bone marrow immunohistochemistry.

Patients in either group could receive a second course of rituximab 6 months after the first. The primary endpoint was 6-month minimal residual diseasefree complete remission rates with concurrent treatment vs cladribine monotherapy in the delayed group. THe delayed group did better nad ahd less toxicity. In the trial, 68 patients with purine analognaive classic hairy cell leukemia were randomly assigned to receive 0.15 mg/kg of cladribine intravenously on days 1 to 5 with eight weekly doses of rituximab at 375 mg/m2 started on day 1 (concurrent group, n = 34) or 6 months later after detection of minimal residual disease in their blood (delayed group, n = 34). Minimal residual disease tests included blood and bone marrow flow cytometry and bone marrow immunohistochemistry.

Patients in either group could receive a second course of rituximab 6 months after the first. The primary endpoint was 6-month minimal residual disease-free complete remission rates with concurrent treatment vs cladribine monotherapy in the delayed group, which favored the concurrent group, but with more thrmbocytopenia..
The investigators concluded: “Achieving minimal residual disease-free complete remission of hairy cell leukemia after first-line cladribine is greatly enhanced by concurrent rituximab and less so by delayed rituximab. Longer follow-up will determine if minimal residual disease-free survival leads to less need for additional therapy or cure of hairy cell leukemia.”

NCCN lists single-agent cladribine or pentostatin in first line and a purine analog with rituximab for recurrent or refractory disease only. and Elitek, not in combination.

Jones G, Parry-Jones N, Wilkins B, Else M, Catovsky D, British Committee for Standards in Haematology. Revised guidelines for the diagnosis and management of hairy cell leukaemia and hairy cell leukaemia variant. Br J Haematol. 2012 Jan;156(2):186-95. [60 references]

Jones G, Parry-Jones N, Wilkins B, et al. Revised guidelines for the diagnosis and management of hairy cell leukaemia and hairy cell leukaemia variant. Br J Haematol 2012; 156:186.

Hagberg H, Lundholm L. Rituximab, a chimaeric anti-CD20 monoclonal antibody, in the treatment of hairy cell leukaemia. Br J Haematol 2001; 115:609.

Robak T. Current treatment options in hairy cell leukemia and hairy cell leukemia variant. Cancer Treat Rev 2006; 32:365.

Arons E, Suntum T, Stetler-Stevenson M, Kreitman RJ. VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy. Blood 2009; 114:4687.

Robak T. Hairy-cell leukemia variant: recent view on diagnosis, biology and treatment. Cancer Treat Rev 2011; 37:3.

Grever MR, Abdel-Wahab O, Andritsos LA, et al. Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia. Blood 2017; 129:553.

https://www.ascopost.com/news/march-2020/first-line-cladribine-with-concurrent-or-delayed-rituximab-for-hairy-cell-leukemia/

nccn, hcl-1, A- 2020

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Sorafenib for desmoid tumors – pro

M Levin, MD — Mon, 17 Dec 2012 16:29:33 +0000

Desmoid tumors, also called aggressive fibromatosis, deep musculoaponeurotic fibromatosis, and fibrosarcoma grade I of the desmoid type, do not generally metastasize but can cause pain and compromise organs. Few treatments for this condition are well established, although many novel agents are being studied. Among them is Nexavar (sorafenib). The basis for the interest in this drug is that it appears to inhibit MPNST cell growth in vitro.

A recent study of sorafenib in children with neurofabromatosis was not able to establish the minmally tolerated dose. A series from Sloan Kettering used sorafenib as first-line therapy in 11/26 patients and the remaining 15/26 had received a median of 2 prior lines of therapy. Twenty-three of 26 patients had shown evidence of progressive disease by imaging, whereas 3 patients had achieved maximum benefit or toxicity with chemotherapy. Sixteen of 22 (∼70%) patients reported significant improvement of symptoms. At a median of 6 months (2-29) of treatment, the best response evaluation criteria in solid tumors (RECIST) 1.1 response included 6/24 (25%) patients with partial response (PR), 17/24 (70%) with stable disease, and 1 with progression and death. NCCN lists sorafenib on p. SARC-E and references the Goundar paper as the basis for its recommendation.

See also here for a more general discussion of chemotherapy for desmoid tumors.

Other options, see here and here and here

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CLINICAL SUMMARY:
39 year-old woman who had been treated with Doxil and experimental therapies of fibromatosis adn nwo Nexvar is being proposed.

REFERENCES:
23.Ambrosini G, Cheema HS, Seelman S, et al. Sorafenib inhibits growth and mitogen-activated protein kinase signaling in malignant peripheral nerve sheath cells. Mol Cancer Ther. Apr 2008;7(4):890-6.

Kim A, Dombi E, Tepas K, Fox E, Martin S, Wolters P, Balis FM,Phase I trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type I and plexiform neurofibromas.Pediatr Blood Cancer. 2012 Sep 7.

Current Perspectives on Desmoid Tumors: The Mayo Clinic ApproachCancers 2011, 3, 3143-3155

Gounder MM, Lefkowitz RA, Keohan ML, et al. Activity of Sorafenib against desmoid tumor/deep fibromatosis. Clin Cancer Res 2011; 17:4082.

nccn, Soft TIssue Sarcoma, 2012

Revlimid and Rituxan for maintenance for lymphoma – pro

M Levin, MD — Thu, 27 Sep 2012 11:52:02 +0000

Recent studies suggest that lanalidomide and rituxan are effective in relapsed or refractory lymphomas. Revlimid, in particular, shows effectiveness for maintenance in myeloma. Because both drugs are well tolerated, this created an interest in studying their effectiveness for maintenance. Currently, maintenance is not standard for most lymphomas, including Diffuse Large B Cell lymphoma. Lenalidomide alone is still in studies, for example, Maintenance Lenalidomide in Lymphoma, NCT01575860.

N. M. Reddy, R. Simmons, M. Caldwell, M. H. Jagasia, D. S. Morgan, S. I. Park, J. P. Greer, K. L. Richards; Vanderbilt University Medical Center, Nashville, TN; University of North Carolina at Chapel Hill, Chapel Hill, NC A phase II randomized study of lenalidomide or lenalidomide and rituximab as maintenance therapy following standard chemotherapy for patients with high/high-intermediate risk diffuse large B-cell lymphoma. J Clin Oncol 29: 2011 (suppl; abstr TPS138)
Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M.
Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial.Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6.

Wang M, Fayad L, Wagner-Bartak N, Zhang L, Hagemeister F, Neelapu SS, Samaniego F, McLaughlin P, Fanale M, Younes A, Cabanillas F, Fowler N, Newberry KJ, Sun L, Young KH, Champlin R, Kwak L, Feng L, Badillo M, Bejarano M, Hartig K, Chen W, Chen Y, Byrne C, Bell N, Zeldis J, Romaguera J Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial.Lancet Oncol. 2012 Jul;13(7):716-23.
Eva Kimby Biological Therapy Doublets: Pairing Rituximab with Interferon, Lenalidomide, and Other Biological Agents in Patients with Follicular Lymphoma Current Hematologic Malignancy Reports September 2012, Volume 7, Issue 3, pp 221-227

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Zevalin and Rituxan for relapsed large cell lymphoma or for consolidation – pro

M Levin, MD — Fri, 14 Sep 2012 15:11:19 +0000

Zevalin, 90Y-ibritumomab tiuxetan, is a novel radioimmunotherapeutic agent approved forthe treatment of relapsed or refractory, low-grade or follicular B-cell non-Hodgkin’s lymphoma (NHL). Zevalin is also indicated for the treatment of previously untreated follicular NHL in patients who achieve a partial or complete response to first-line chemotherapy.

90Y-ibritumomab tiuxetan consists of a murine monoclonal antibody covalently attached to a metal chelator, which stably chelates 111In for imaging and 90Y for therapy. It is often used for other than first line of treatment for lymphoma.

A recent guideline states experts’ consensus: “It is the opinion of the Hematology Disease Site Group that the benefit of 90Y-ibritumomab tiuxetan radioimmunotherapy may be generalizable to other relapsed or refractory indolent non-Hodgkin’s lymphomas previously treated with rituximab….but not CLL.

F. Morschhauser, T. Illidge, D. Huglo et al., “Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation,” Blood, vol. 110, no. 1, pp. 54–58, 2007.

Leung M, Haynes AE, Stevens A, Meyer RM, Imrie K, Hematology Disease Site Group. Ibritumomab tiuxetan in lymphoma: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2006 Jul 17. 42 p. (Evidence-based series; no. 6-17). [44 references]

Giulia Motta, Michele Cea, Eva Moran, Federico Carbone, Valeria Augusti, Franco Patrone, and Alessio Nencioni Monoclonal Antibodies for Non-Hodgkin’s Lymphoma: State of the Art and Perspectives Clinical and Developmental ImmunologyVolume 2010 (2010),

Yang DH, Kim WS, Kim SJ, Kim JS, Kwak JY, Chung JS, Oh SY, Suh C, Lee JJ. Pilot trial of yttrium-90 ibritumomab tiuxetan consolidation following rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy in patients with limited-stage, bulky diffuse large B-cell lymphoma. Leuk Lymphoma. 2012 May;53(5):807-11.

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How to follow Diffuse Large Cell Lymphoma after completing treatment

M Levin, MD — Fri, 07 Sep 2012 22:20:18 +0000

Athough CT remains the gold standard for the staging and follow-up of malignant lymphomas, 18F-FDG PET has a potential role in accurately staging disease and in predicting response to therapy. On the other, guidelines do not recommend MRI for surveillance. The most common lymphoma is Diffuse Large B0cell Lymphoma(DLBCL). 2012 NCCN Guidelines for DLBCL on p. BCEL-4 recommend CT no more often than every 6 months for 2 years after completion of treatment, then only as clinically indicated. In contrast to the North American guidelines, the European Society of Medical Oncology (ESMO) in 2007 specifically advises against routine imaging except to evaluate residual disease. These guidelines recommend:

PET scan at end of treatment, if available
Minimal radiologic examinations in patients with DLBCL at 6, 12, and 24 months after end of treatment, when indicated by site of disease
In regard to followup, a recent study showed that a negative PET scan after completion of therapy does not exclude the presence of residual microscopic disease and does not indicate complete remission. The majority of studies evaluating FDG-PET in lymphoma include patients with diffuse large B-cell non-Hodgkin’s lymphoma (NHL) or Hodgkin’s disease. There are limited data available on the role of PET in other histologies.

A negative PET scan at the end of therapy appears to provide favorable prognostic information. Persistently positive PET scans at the end of therapy, or in follow-up, warrant close follow-up or additional diagnostic procedures, since some of those patients may remain in prolonged remission.

The Imaging Subcommittee of the International Harmonization Project (IHP) in Lymphoma developed guidelines for performing and interpreting positron emission tomography (PET) for treatment assessment in patients with lymphoma. The new recommendations, targeting both clinical practice and clinical trials, are published in the January 22 Early Release issue of the 2007 al of Clinical Oncology. They are based on experts’ consensus and not randomized evidence.

Specific recommendations related to followup are:

After treatment completion, PET should be performed at least 3 weeks, and preferably 6 to 8 weeks, after chemotherapy or chemoimmunotherapy, and 8 to 12 weeks after radiation or chemoradiotherapy. Noncontrast PET/CT can be used instead of contrast-enhanced diagnostic CT to follow-up patients with lymphoma, although patients with hepatic or splenic involvement should continue to receive contrast-enhanced diagnostic CT. Attenuation-corrected PET is much preferred over nonattenuation-corrected scans.

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PET for lymphomas – pro

M Levin, MD — Wed, 05 Sep 2012 16:54:20 +0000

Although CT remains the gold standard for the staging and follow-up of malignant lymphomas, 18F-FDG PET has a potential role in accurately staging disease and in predicting response to therapy. This role has the potential to affect both the initial choice of chemotherapy and the decision to alter management based on the initial response to therapy . PET performed early in a chemotherapeutic regimen has demonstrated a role in identifying patients who will experience relapse and may require further treatment, but attention to the timing of the scan in relation to chemotherapy and growth factors is crucial. Many studies have used subjective grading systems to assess response and have evaluated progression-free survival on the basis of negative or positive findings on follow-up scans. Further studies should focus on measuring response on the basis of SUV: Determining a cutoff value when assessing the percentage of change in SUV may improve the prognostic value of interim PET. Because most studies have shown variable SUVs among both aggressive and indolent lymphomas, the usefulness of a follow-up scan hinges on the existence of a pretherapy scan demonstrating 18F-FDG–avid disease. The role of 18F-FDG PET for indolent lymphomas, like CLL, remains unclear, and further studies have to be designed to investigate the role of PET for specific histologic types. NCCN (p.127) recommends PET for restaging of large cell lymphoma.

Freudenberg LS, Antoch G, Schutt P, et al. FDG-PET/CT in re-staging of patients with lymphoma. Eur J Nucl Med Mol Imaging. 2004;31:325–329

Yuliya S. Jhanwar and David J. Straus The Role of PET in Lymphoma Journal of Nuclear Medicine Vol. 47 No. 8 1326-1334, 2006

Bruce D. Cheson MD, Non-Hodgkin’s Lymphomas: New Insights and Therapeutic Strategies
Staging and Evaluation of the Patient with Lymphoma
Hematology/Oncology Clinics of North America
Volume 22, Issue 5, October 2008, Pages 825-837

Low Grade Follicular Lymphoma Treatment – pro

M Levin, MD — Wed, 05 Sep 2012 16:28:42 +0000

Lay Summary: I review options for follicular lymphoma treatment.

Patients with low-grade non-Hodgkin’s lymphoma (NHL) have a median survival of 4-8 years from diagnosis and a cause-specific survival of about 10 years. Radiotherapy can be curative in a small proportion of patients with very localized disease, but the majority of patients have advanced disease at diagnosis and it is not clear that any current therapy is curative in this situation. While in many instances patients with high-grade NHL are cured by chemotherapy, those with low-grade NHL, despite impressive response rates, almost invariably relapse. A ‘watch-and-wait’ strategy can therefore delay the onset of chemotherapy by 2-3 years, without affecting survival. Results with autologous stem cell transplantation have been similarly disappointing to date. Rituximab is a human-mouse chimeric monoclonal antibody that represents a novel approach to treatment of low-grade NHL, targeting malignant cells without the side effects associated with chemotherapy. A pivotal study has demonstrated a response rate of 56% in relapsed or refractory low-grade NHL. The relatively benign side-effect profile means rituximab can be used early in the disease process, and in combination with chemotherapeutic regimens and autologous transplantation. Ongoing and future studies will define the optimal role of rituximab in treatment of low-grade NHL.

In addition to the R-CVP regimen, NCCN 201 on p. FOLL_B, 1 cites R-CHOP, FR(fludarabine/rituximab), radioimmunotherapy, RFNDP, bendamustine/rituximab, rituximab alone.

Angioimmunoblastic T-cell – pro

M Levin, MD — Tue, 04 Sep 2012 15:13:14 +0000

Angioimmunoblastic T-cell lymphoma (AILD) is considered a variety of T-cell lymphoma, which usually occurs in adults. Patients present with profound lymphadenopathy, fever, night sweats, weight loss, skin rash, a positive Coomb’s test, and polyclonal hypergammaglobulinemia. It is quite rare and no standrd approach has beend efined. Angioimmunoblastic T-cell lymphoma was formerly called angioimmunoblastic lymphadenopathy with dysproteinemia. Characterized by clonal T-cell receptor gene rearrangement, this entity is managed like diffuse large cell lymphoma. Opportunistic infections are frequent due to an underlying immune deficiency. Doxorubicin-based combination chemotherapy is recommended as it is for other aggressive lymphomas. Myeloablative chemotherapy and radiation therapy with autologous peripheral stem cell support has been described in anecdotal reports. Occasional spontaneous remissions and protracted responses to steroids only have been reported. A few patients may progress to an EBV-positive diffuse large B-cell lymphoma. I have not found any studies reporting the use of autologous SC for this entity. A recent (2006) retrospective review of ASCT in T-cell lymhomas reported good results in 6 angioimmunoblastic lymphoma patients. All angioimmunoblastic T-cell lymphoma (AILT) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients achieved CR; 5 of 6 have remained disease free for more than 3 years. However, this is a very small sample.

A search of current trials reveals a variety of investigtional approaches to this disease, including stem cell transplant in second remission.

http://clinicaltrials.gov/ct/search?term=%22T-cell+lymphoma%22+%5BCONDITION%5D+AND+angioimmunoblastic+%5BALL-FIELDS%5D&submit=Search

Reimer P, Schertlin T, Rüdiger T, et al.: Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J 5 (4): 304-11, 2004.

Pautier P, Devidas A, Delmer A et al. Angioimmunoblastic-like T-cell non Hodgkin’s lymphoma: outcome after chemotherapy in 33 patients and review of the literature. Leuk Lymphoma 1999; 32: 545–552

Yamazaki T, Sawada U, Kura Y, et al.
Treatment of high-risk peripheral T-Cell lymphomas other than anaplastic large-cell lymphoma with a dose-intensified CHOP regimen followed by high-dose chemotherapy
ACTA HAEMATOLOGICA 116 (2): 90-95 2006

Maintenance Rituxan – pro

M Levin, MD — Mon, 03 Sep 2012 02:21:39 +0000

Lay Summary: Maintenance rituximab is becoming more common although questions remain about its benefit for DLBCL.

The impact of maintenance treatment with rituximab on overall survival is one of the most important open questions for patients with indolent non-Hodgkin lymphoma. Recent randomized trials performed by the German Low Grade Lymphoma Study Group (GLSG) and by the EORTC demonstrated the superiority of rituximab maintenance after immunochemotherapy and after chemotherapy compared with observation alone.

Clinical trials have demonstrated prolongation of progression-free survival and, in some cases, increased survival when “maintenance” rituximab is given following rituximab induction, chemotherapy induction, or rituximab/chemotherapy (relapsed setting).

A recent guideline says this about maintenance rituximab for low grade lymphoma: “For previously treated patients with follicular or other indolent B-cell-histology lymphoma (such as mantle cell lymphoma, marginal zone lymphoma, and lymphoplasmacytoid lymphoma), excluding small lymphocytic lymphoma (SLL):
However, a Canadian guideline does recommend this approach and it is becoming the predominant approach in clinical practice.NCCN also lists it as category 1 recommendation on p. FOLL-B. First line extended therapy – If initially treated with single-agent Rituxan, consolidation with Rituximab 375mg/m2 one dose q 12 weeks is supported. FDA approved Rituxan as a maintenance therapy for patients with advanced follicular lymphoma in January of 2011. Farthermore, NCCN marginal lymphoma guideliens take one to the follicular lymphoma pages, where maintenance is recommended

On June 13, 2011, at the 16th Congress of the European Hematology Association in London, there was presented a study of maintenance rituximab after responding to initial therapy. It was restricted to elderly patients and showed that maintenance doubled the duration of remission doubled. Overall survival at 4 years also improved with rituximab maintenance, and experts suggest it should become the new standard of care. At 4 years, 57% of the patients treated with rituximab were still in in remission, compared with 26% of those treated with interferon (P = .0117). ” This study has not yet been published. The schedule is not NCCN prescribed and various schedules have been reported. NCCN recommends up to 2 years of maintenance therapy on FOll-B, 1

For large cell lymphoma, NCCN does NOT recommend maintenance Rituxan. Rituxan after CHOP, but not after R-CHOP, significantly prolongs TTF, but fails to prolong OS, possibly due to a delayed pattern of relapse and/or the efficacy of rituximab in the salvage setting(An Intergroup E4494/C9793 update). NCCN on p. BCEL specifically states that and does not recommend it.

For mantle cell lymphoma, NCCN also does not recommend maintenance. On June 13, 2011, at the 16th Congress of the European Hematology Association in London, there was presented a study of maintenance rituximab after responding to initial therapy. It was restricted to elderly patients and showed that maintenance doubled the duration of remission doubled. Overall survival at 4 years also improved with rituximab maintenance, and experts suggest it should become the new standard of care. At 4 years, 57% of the patients treated with rituximab were still in in remission, compared with 26% of those treated with interferon (P = .0117). ” This study has not yet been published.

NCCN recommends it for marginal zone lymphoma

NCCN, MZA-A, 2 2017

NCCN.ORG, NHLm follicular 2017

NCCN, MANT-4 2017

Revised 2/4/2012

Imrie K, Stevens A, Meyer R, Hematology Disease Site Group. Rituximab in lymphoma and chronic lymphocytic leukemia: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2005 Dec 22. 46 p. (Evidence-based series; no. 6-8). [65 references]

S. J. Horning
Optimizing Rituximab in B-Cell Lymphoma
J. Clin. Oncol., February 20, 2005; 23(6): 1056 – 1058.

John D. Hainsworth, Sharlene Litchy, Don W. Shaffer, Van L. Lackey, Manuel Grimaldi, F. Anthony Greco, Maximizing Therapeutic Benefit of Rituximab: Maintenance Therapy Versus Re-Treatment at Progression in Patients With Indolent Non-Hodgkin’s Lymphoma—A Randomized Phase II Trial of the Minnie Pearl Cancer Research Network
Journal of Clinical Oncology, Vol 23, No 6 (February 20), 2005: pp. 1088-1095

Habermann TM, Weller EA, Morrison VA, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 2006;24:3121–3127.

Chang JE, Peterson C, Choi S, Eickhoff JC, Kim K, Yang DT, Gilbert LA, Rogers ES, Werndli JE, Huie MS, McFarland TA, Volk M, Blank J, Callander NS, Longo WL, Kahl BS. VcR-CVAD induction chemotherapy followed by maintenance rituximab in mantle cell lymphoma: a Wisconsin Oncology Network study.Br J Haematol. 2011 Oct;155(2):190-7.

Revlimid for Chronic lymphocytic leukemia – pro

M Levin, MD — Mon, 03 Sep 2012 02:04:36 +0000

Lay Summary: Revlimid is promising for CLL.

Revlimid is an orally administered derivative of thalidomide, which is a very active agent for the treatment of multiple myeloma but has serious side effects, especially thromboembolism. Revlimid is reported to have less toxicity than thalidomide but retains antimyeloma effects. Revlimid has recently been approved by the FDA for review of treatment of myelodysplastic syndromes (MDS) wih a 5q- mutation and for first line treatment of multiple myeloma in conjunction with dexamethasone. Revlimid is in clinical trials for the evaluation of treatment for other hematologic cancers including CLL.

There are many studies supporting effectiveness of Revlimid, although most of them are small and presented in the abstract form.

Researchers from the Roswell Park Cancer Center and the Toronto Sunnybrook Regional Cancer Center have reported that Revlimid has significant activity in CLL. This study was also presented at the 2005 meeting of the American Society of Hematology in December 2005. Thalidomide has also demonstrated activity when combined with Fludara for initial treatment of CLL. This was a small study involving only 16 patients, but the complete response rate was over 50%.

The study presented at ASH 2005 and ASCO 2006 involved 29 patients with relapsed or refractory CLL. More than 50% has failed Rituxan combinations and more than 50% had failed fludarabine combinations. The complete response rate was 15%, the partial response rate was 53% and an additional 15% had stable disease. Two patients had complete molecular responses. The most common side effects reported were fatigue, neutropenia and thrombocytopenia. Approximately 60% had “flare reaction”—described as tender swelling of lymph nodes and rash—which was successfully treated with steroids. In-vitro studies showed an increased number of natural killer cells but no increase in apoptosis.

In 2008, Celgene reported two REVLIMID (lenalidomide) Phase II studies at the 50th American Society of Hematology Meeting. Both demonstrated high response rates and manageable side effects in patients previously untreated with symptomatic chronic lymphocytic leukemia (CLL). The studies demonstrated greater than 90 percent disease control across all evaluable patients. In 2009, at ASH, there was presented a phase II study of Rituxan. Revlimid combination conducted at MD Anderson Cancer Center demonstrated a 64 percent overall response after 12 cycles, including the observation of complete responses. In 2008, at ASH, there was presented a phase II study of Rituxan. Revlimid combination conducted at MD Anderson Cancer Center demonstrated a 64 percent overall response after 12 cyces, including the observation of complete responses.

It is also listed by the Drugdex compendium for CLL. The most recent noteworthy paper was in Blood 2011. Sixty patients with CLL age 65 years and older received treatment with lenalidomide orally 5 mg daily for 56 days, then titrated up to 25 mg per day as tolerated. Treatment was continued until disease progression. At a median follow-up of 29 months, 53 patients (88%) are alive and 32 patients (53%) remain on therapy. Estimated 2-year progression-free survival is 60%. The overall response rate to lenalidomide therapy is 65% including 10% complete response, 5% complete response with residual cytopenia, 7% nodular partial response, and 43% partial response. These are very good results for the limited reported toxicity in the ederly population.

Miller K, Czuczman MS, Dimicli L, et al. Lenalidomide (L) induces high response rates with molecular remission in patients (pts) with relapsed (rel) refractory (ref) chronic lymphocytic leukemia (CLL). Proceedings from the 42nd annual meeting of the American Society of Clinical Oncology. Atlanta, Ga. 2006. Abstract # 6605.

Chanan-Khan AA, Miller KC, DiMicheli L, et al. Results of a phase II study of lenalidomide (L) (Revlimid) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Blood 2005;135a, abstract # 447.

Chanan-Khan A, Miller KC, Takeshita K, et al. Results of a phase 1 clinical trial of thalidomide in combination with fludarabine as initial therapy for patients with treatment-requiring chronic lymphocytic leukemia (CLL). Blood. 2005;106:3348-3352.

Chanan-Khan A, Miller KC, Musial L, et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase II study. Journal of Clinical Oncology. 2006;24:5343-5349.

Chen C, Paul H, Xu W, et al. A phase II study of lenalidomide in previously untreated, symptomatic chronic lymphocytic leukemia (CLL). Blood. 2008;112:23, abstract number 44.

Kornblau SM, Burger JA, Ferrajoli A.et al, Lenalidomide (REVLIMID) as initial therapy of elderly patients with chronic lymphocytic leukemia.Blood. 2011 Jul 1.