Cancer Treatment Today » Large B-cell Lymphoma

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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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

Autologous and allogeneic stem cell transplantation for diffuse large cell lymphoma (NHL) – pro

M Levin, MD — Sun, 02 Sep 2012 14:56:12 +0000

Summary: NHL is currently the second most frequent indication for autologous hematopoietic stem cell transplantation. It is not a useful treatment option for all patients with NHL, but in certain circumstances, autologous stem cell transplantation does provide patients the best opportunity for cure.

Diffuse large-cell lymphoma is the most common form of NHL, and autologous stem cell transplantation has been shown to be beneficial in some subsets with this illness. For patients with diffuse large-cell lymphoma who relapse from a CR but remain chemotherapy-responsive, autologous transplantation is the treatment of choice. The most significant study supporting transplantation is the PARMA study by Philip et al. Patients were randomized to autologous stem cell transplantation versus conventional-dose chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin (DHAP) if the patient responded to two initial cycles of DHAP. The event-free survival at 5 years was 46% for the transplant arm and 12% for the conventional therapy arm (p = 0.001). Overall survival was 53% for transplant and 32% for the conventional therapy group (p = 0.038). In addition to transplant being shown to be beneficial in this group of patients, additional analysis has demonstrated that an initial remission of fewer than 12 months is an adverse prognostic indicator.

There are also trials that have found contradictory results. Reyes et al. in the LNH93-3 trial randomized 370 patients to standard chemotherapy or autologous transplantation after an abbreviated standard-dose induction regimen. They found the 3-year event-free survival for the hematopoietic stem cell transplant group was 41% versus 54% for the standard therapy arm (p = 0.01). Overall survival was also in favor of standard therapy with 63% disease-free survival versus 47% in the transplanted group (p = 0.003) [62]. A trial by Verdonck et al. randomized 69 patients who had achieved a partial response to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to additional CHOP or autologous bone marrow transplantation. The 4-year event-free survival was 53% for the CHOP arm and 41% for the transplantation arm. Disease-free survival at 4 years was 72% for the CHOP group and 60% for transplantation. The reason for the disrepancy is not well understood but these were smaller studies than the PARMA study.

At the present time, high-risk patients who achieve a CR after a full course of standard-dose chemotherapy and have a high risk for relapse may derive the most benefit from stem cell transplantation. The second accepted group is those who evidence chemoresponsiveness after relapse and this is stated in the NCCN guidelines. No additional trials are planned and the Parma results have been accepted as standard therapy.

2011 NCCN on p. BCEL-6 recommends an autologous transplant.

As far as allogeneic, a recent guideline says: “Allogeneic stem cell transplantation is an option for eligible chemosensitive patients with refractory or relapsed AH-NHL who are not candidates for autologous stem cell transplantation or who have a syngeneic (identical twin) donor.” NCCN BCEL-6(2011) says tha llogeneic transplantation is in selected cases and a note explains that such cases include mobilization faiure and persiistent bone marrow invovlement”. All in all, I consider guidelines to mildy support allogeneic transpalntation for relapsed DLCL.

For patients who failed an autologous transplant, 2012 ESMO guideline says: “Allogeneic stem cell transplantation (allo-SCT) should be considered in selected patients failing autologous stem cell transplantation or with very poor risk factors at relapse”.

Zahid U, Akbar F, Amaraneni A, et al. A Review of Autologous Stem Cell Transplantation in Lymphoma. Curr Hematol Malig Rep. 2017;12(3):217–226. doi:10.1007/s11899-017-0382-1

Imrie K, Rumble RB, Crump M, Advisory Panel on Bone Marrow and Stem Cell Transplantation, Hematology Disease Site Group. Stem cell transplantation in adults: recommendations. Toronto (ON): Cancer Care Ontario Program in Evidence-based Care; 2009 Jan 30. 78 p. (Recommendation report; no. 1). [66 references]

Vikas Gupta et al, Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns Blood February 24, 2011 vol. 117 no. 8 2307-2318

van Kampen RJW, Canals C, Schouten HC, et al. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-hodgkin’s lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European group for blood and marrow transplantation registry. J Clin Oncol 2011;29:1342-1348.

Thomson KJ, Morris EC, Bloor A, et al. Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-hodgkin’s lymphoma. J Clin Oncol 2009;27:426-

Gemzar and Navelbine salvage for lympnoma – pro

admin — Sun, 02 Sep 2012 00:47:15 +0000

Gemcitabine, vinorelbine and prednisone or otehr drugs are being investigated to treat refractory or relapsed aggressive non-Hodgkin lymphomas (NHL).
Lay Summary: Gemcitabine and vinorelbine are somewhat effective but toxic when few options remain, but more investigation is needed.

The optimum therapy for patients with relapsed or refractory aggressive NHL not qualifying for platinum-based and/or high-dose chemotherapy is not known. In one prospective phase II study evaluating a regimen consisting of gemcitabine (1 g/m2, days 1 and 8), vinorelbine (30 mg/m2, days 1 and 8) and prednisone (100 mg/day, days 1-8) (GVP) given every 21 days, there was substantial activity in poor prognosis relapsed or refractory aggressive lymphomas. It was generally well tolerated, but haematological toxicity is dose limiting. Several other studies yilded similar results.

One has to conclude that despite these results the treatment is still experimental as it is being studies in various studies with otehr agents added and a prospective phase III trial is necessary.

Efstathios S. Papageorgiou, Panagiotis Tsirigotis, Meletios Dimopoulos, Nikolaos Pavlidis, George Fountzilas, Sotirios Papageorgiou, Theofanis Economopoulos (2005) Combination chemotherapy with gemcitabine and vinorelbine in the treatment of relapsed or refractory diffuse large B-cell lymphoma: a phase-II trial by the Hellenic Cooperative Oncology Group European Journal of Haematology 75 (2), 124–129.

A. Spencer, K. Reed and C. Arthur. (2007) Pilot study of an outpatient-based approach for advanced lymphoma using vinorelbine, gemcitabine and filgrastim. Internal Medicine Journal 37:11, 760–766

Fatih M. Uckun, Sanda Morar and Sanjive Qazi. (2006) Vinorelbine-based salvage chemotherapy for therapy-refractory aggressive leukaemias. British Journal of Haematology 135:4, 500–508

Rituximab, gemcitabine, oxaliplatin salvage chemotherapy for Non-Hodgkin’s Lymphoma – pro

M Levin, MD — Fri, 31 Aug 2012 13:38:16 +0000

The study that suggests that the combination of gemcitabine, rituximab, oxaliplatin, and pegfilgrastim iseffective as a salvage regimen for relapsed non-Hodgkin’s lymphoma (NHL) and is less toxic was presented at the 2008 meeting of the American Society of Clinical Oncology in Chicago May 30-June 2.It included 37 patients with relapsed aggressive NHL treated with gemcitabine, rituximab, oxaliplatin (GROC) and pegfilgrastim given every 14 days. The results were compared with other salvage regimens. Anotheh study od forty-six patients with relapsed or refractory B-cell lymphoma who received up to eight cycles of R-GemOx (rituximab 375 mg/m2 on day 1, gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 on day 2). showed that after four cycles of R-GemOx, the overall response rate was 83% [50% complete response (CR)/unconfirmed CR (CRu)]. High CR/CRu rates were observed in all histological subtypes. Among responders, the probability of being disease free for 2 years was 62% and treatment was generally well tolerated. There were no patients who failed transplant in these studies.

Reliable evidence shows that experts consider farther studies necessary and this defines this regimen as being experimental as per most plan languages.

Cabanillas F, Liboy I, Rodriguez-Monge E, et al. GROC (gemcitabine, rituximab, oxaliplatin combination) plus pegfilgrastim is less toxic and as active as DHAP and ESHAP for relapsed aggressive non-Hodgkin’s lymphoma (NHL). Journal of Clinical Oncology. 2008;26:abstract 8530.

T El Gnaoui , J Dupuis , K Belhadj , J-P Jais , A Rahmouni , C Copie-Bergman , I Gaillard , M Diviné , I Tabah-Fisch , F Reyes , and C Haioun
Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy
Annals of Oncology Advance Access published on May 11, 2007, DOI 10.1093/annonc/mdm133.

Mozobil – pro

M Levin, MD — Fri, 31 Aug 2012 13:33:56 +0000

Mozobil, a novel small molecule CXCR4 chemokine receptor antagonist, has been shown in multiple earlier studies to rapidly and effectively increase the number of stem cells in circulation in the blood in patients with non-Hodgkin’s lymphoma and multiple myeloma. Once circulating in the blood, stem cells can be collected for use in an autologous stem cell transplant. While G-CSF is the standard mobilizing agent for PBSC donors, it is associated with some significant side effects and requires a multi-day dosing regimen. The other cytokine approved for stem cell mobilization, granulocyte-macrophage colony stimulating factor (GM-CSF), alters graft composition and may reduce the development of graft-versus-host disease (GVHD), but a significant minority of donors fails to provide sufficient CD34+ cells with GM-CSF and some experience unacceptable toxicity. Mobizil may be more effective and is better tolelrated but it is usually sued with G-CSF and toxicity advantages may not be clinically relevant. Patients treated with G-CSF and Mozobil were three times more likely than patients treated with G-CSF alone to reach the target threshold for collection with four or fewer days apheresis.

On December 15, 2008, U.S. Food and Drug Administration has granted marketing approval for Mozobil (plerixafor injection), a drug intended to be used in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the bloodstream for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). The product has also been granted orphan drug designation. Mozobil is intended to be used in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple myeloma.

Use of Mozobil in other diagnoses is off-label. A number of ongoing trials are exploring various facets of Mozobil therapies but do not include a specific trial for neuroblastoma. While it would be reasonable to conclude that Mozobil is safe and effective in codnitions other than indicated, this has not been explored and is not known.

Inpharma, Volume 1, Number 1600, 2007-08-11 , pp. 6-6(1)

Giralt S, Costa L, Schriber J, et al. Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations. Biol Blood Marrow Transplant. 2014;20(3):295-308.
Costa LJ, Miller AN, Alexander ET, et al. Growth factor and patient-adapted use of plerixafor is superior to CY and growth factor for autologous hematopoietic stem cells mobilization. Bone Marrow Transplant. 2011;46(4):523-528.

Mozobi, prescribing informatiohttp://www.mozobil.com/document/Mozobil_PM.pdfn, 2018

Keating GM. Plerixafor: a review of its use in stem-cell mobilization in patients with lymphoma or multiple myeloma. Drugs. 2011 Aug 20;71(12):1623-47.

Central Nervous System Prophylaxis for Diffuse Large Cell Lymphoma – pro

M Levin, MD — Tue, 28 Aug 2012 17:19:43 +0000

There remains an open question about whether intermediate risk lymphomas, such as diffuse large cell lymphomas, with poor risk factors (such as extranodal involvement or certain mutatiosn or markers) require prophylaxis against CNS involvement alongside IV chemotherapy, because there is a higher risk of the involvement in these sanctuary sites in these cases. Such prophylaxis can be intrathecal or high dose methotrexate with follinic acid rescue and cytarabine. The consensus is that some, such as testicular lymphoma, should and some should not. ESMO writes: “Patients with high–intermediate- and high-risk IPI, especially those with more than one extranodal site or elevated LDH are at higher risk of CNS relapse. CNS prophylaxis should be recommended in this population but intrathecal injections of methotrexate are probably not an optimal method. Whether some specific involvement sites such as paranasal sinus, upper neck or bone marrow should receive prophylaxis remains to be established. Testicular lymphoma must receive CNS prophylaxis”. The National Comprehensive Cancer Network (www.nccn.org) guidelines for diffuse large B-cell (DLBCL) lymphoma recommend CNS prophylaxis with 4 to 8 doses of intrathecal methotrexate (MTX) and/or cytarabine for patients with aggressive lymphomas who have paranasal sinus, testicular, epidural, bone marrow, 2 extranodal site involvement, or HIV lymphomas. A recent(2012) review of the impact of CNS prophylaxis in DLBCL patients treated with R-CHOP at a tertiary care center over a 7-year period concluded that in the era of R-CHOP there may not be a need for CNS prophylaxis with the exception of testicular lymphoma.

H. Takasaki et al, Intrathecal methotrexate prophylaxis and central nervous system relapse in patients with diffuse large B-cell lymphoma following rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone Leukemia & Lymphoma Volume 56, 2015 – Issue 3

H. Tilly, M. Dreyling, Diffuse large B-cell non-Hodgkin’s lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol (2010) 21 (suppl 5): v172-v174.

nccn, NHL, 2018

Hany R et al, Impact of central nervous system (CNS) prophylaxis on the incidence and risk factors for CNS relapse in patients with diffuse large B-cell lymphoma treated in the rituximab era: a single centre experience and review of the literature .British Journal of Haematology Article first published online: 31 JUL 2012 DOI: 10.1111/j.1365-2141.2012.09247.x 2012 Blackwell Publishing Ltd

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Revlimid for refractory relapsed B-cell lymphoma – pro

M Levin, MD — Mon, 27 Aug 2012 20:34:37 +0000

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.

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.

Many studies are now underway to evaluate the activity of Revlimid in combination with rituximab in patients with lymphoma. The initial analysis of the first 46 patients of a 200 patient
phase-II, multi-center open-label clinical study, NHL-003, shows
encouraging results that are consistent with those of the earlier
NHL-002 trial (Abstract #2565). Responses were seen across all
sub-types of NHL. Furthermore, prognostic factors have been identified
that may be predictive of response to REVLIMID monotherapy. The study reported that overall response to single agent lenalidomide was 28%, with 6 responses in the diffuse large B-cell lymphoma group (21%) and 5 in the mantle cell lymphoma group (38%). Ten patients had stable disease (SD). This was reported at ASH in December 2007.

Although some question tolerability of the 25mg dose, there are now several supportive phase II studies adn others are ongoing.

A 2009 paper by Witzig concluded: “Oral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL, warranting further investigation of treatment for indolent NHL.”

Newer studies confirm that lenalidomide is effective for relapsed or refractory large B-cell lymphomas as well.Llenalidomide represented an active drug on aggressive relapsed NHL. There are positive trials in this setting of Revlmid used without rituximab and ones that added rituximab. Monotherapy as well as use with rituximab with lenalidomide showed an activity in term of overall response rate, with acceptable hematological and extrahematological toxicities in relapsed/refractory aggressive NHL.

T. E. Witzig et al, A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma. Ann Oncol (2015) doi: 10.1093/annonc/mdv102

Annalisa Chiappella and Umberto Vitolo. Review Article Lenalidomide in Diffuse Large B-Cell Lymphomas
dvances in Hematology. Volume 2012 (2012), Article ID 498342, 5 pages

http://dx.doi.org/10.1155/2012/498342

Thomas E. Witzig et al,
Lenalidomide Oral Monotherapy Produces Durable Responses in Relapsed or Refractory Indolent Non-Hodgkin’s Lymphoma, JCO November 10, 2009 vol. 27 no. 32 5404-5409

Habermann TM, Lossos IS, Justice G, et al. Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. British Journal of Haematology. 2009;145:344-349.

Vose JM, Zinzini PL, Reeder CB, et al. Confirmation of the efficacy and safety of lenalidomide oral monotherapy in patients with relapsed or refractory diffuse large-B-cell lymphoma: Results of an international study *NHL-003). Blood. 2008;112:103, abstract 268.

M. S. Czuczman, C. B. Reeder, J. Polikoff, N. M. Chowhan, I. Esseessee, R. Greenberg, A. Ervin-Haynes, D. Pietronigro, J. B. Zeldis, T. E. Witzig International study of lenalidomide in relapsed/refractory aggressive non-Hodgkin’s lymphoma. J Clin Oncol 26: 2008 (May 20 suppl; abstr 8509)