Cancer Treatment Today » Non-Hodgkin’s Lymphoma

Azerra for mantle cell lymphoma

M Levin, MD — Sun, 31 Mar 2013 13:07:40 +0000

Azerra (ofatumumab) is a new antibiody against Chronic lymphocytic leukemia( CLL). Preclinical data suggest that it might be more effective than Rituxan in variety of lymphomas. In early clinical trials, ofatumumab demonstrated single-agent activity against chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin’s lymphomas. It was approved by the US Food and Drug Administration for the treatment of CLL that is resistant to both fludarabine and alemtuzumab. In In early clinical trials, ofatumumab demonstrated single-agent activity against CLL and a number of subtypes of B-cell non-Hodgkin’s lymphomas.

Not much is known about using this drug for mantle cell lymphoma. Preclinical comparisons make it appears superior to rituxumab but there are also studies in which it does not. A recent review noted that pre-clinical data suggest improved cell killing for ofatumumab compared with rituximab. Ofatumumab is in a clinical trial for Mantle cell lymphoma: Ofatumumab With or Without Bendamustine for Patients With Mantle Cell Lymphoma Ineligible for Autologous Stem Cell TransplantThis study is being done to understand how to treat Mantle Cell Lymphoma (MCL).

M. Magni presented an abstract in the 2011 ASH conference. It reported that chemotherapy with bendamustine and ofatumumab appears generally safe and well tolerated to date in MCL patients aged ≥ 65 years requiring treatment. Preliminary data about efficacy are encouraging: accrual is ongoing for further evaluation.

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Revlimid and Rituxan for lymphoma maintenance

M Levin, MD — Thu, 27 Sep 2012 11:54:59 +0000

Recent studies suggest that lenalidomide 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. The idea behind maintenance therapy is to supress any remaining or dormant cells and to prolong time to the return of the diseae, or possibly to produce a cure. 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.

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Double Hit Lymphoma

M Levin, MD — Wed, 19 Sep 2012 01:08:21 +0000

Double – hit (DH) lymphomas are a recently discovered subtype of lymphoma that is defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint, for instance a t(14;18)(q32;q21), involving BCL2. In the 2008 WHO classification, they are classified as “B cell lymphoma unclassifiable with features intermediate between Diffuse Large Cell Lymphoma(DLBCL) and Brkitt’s Lymphoma(BL)”. Thus, it is somewhere between intermediate and highly aggressive lymphomas in how it behaves.

In some ways it is similar to Burkitt’s; however, while the diagnosis of Burkitt lymphoma (BL) is generally straightforward, these lymphomas tend to have atypical morphologic and/or immunophenotypic features that overlap with other types of high-grade B-cell lymphoma, particularly diffuse large B-cell lymphoma (DLBCL). They often have an extremely poor prognosis, with a median survival of 6 or so months and represent an entity distinct from both Burkitt’s Lymphoma and DLBCL.

Unfortunately, it is no known how to treat double-hit lymphomas. The prevailing paradigm among oncologists has been to treat more aggressive cancer more aggressively but it is now being questioned. While it is tempting after initial chemotherapy to consolidate with high dose therapy and transplantation, the entity is too new to have accumulated significant published information on response to therapy and role of transplantation. NCCN currently recommends for DLBCL: ”consider high dose therapy Category 2B for complete and incomplete responders in high risk patients”. That seems to be a reasonable approach also to a Double Hit Lymphoma at this time.

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How long to follow after remission of diffuse large cell lymphoma – pro

M Levin, MD — Fri, 07 Sep 2012 19:40:19 +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. On the other hand, guidelines do not recommend PET routinely for surveillance. 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:

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.

As noted, guidelines do not recommend PET for surveillance after that point.

Barrington SF, Kluge R. FDG PET for therapy monitoring in Hodgkin and non-Hodgkin lymphomas. Eur J Nucl Med Mol Imaging. 2017;44(Suppl 1):97-110.

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

Lavely WC, Delbeke D, Greer JP,

NCCN, NHL, BCEL-4, 2018

J. W. Fletcher, B. Djulbegovic, H. P. Soares, B. A. Siegel, V. J. Lowe, G. H. Lyman, R. E. Coleman, R. Wahl, J. C. Paschold, N. Avril, et al.
Recommendations on the Use of 18F-FDG PET in Oncology
J. Nucl. Med., March 1, 2008; 49(3): 480 – 508.

Zelenetz A, Abramson JS, Advani A, et al. NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin’s Lymphomas. Version 2, 2011. Available at: http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf.

Jost L. Newly diagnosed large B-cell non-Hodgkin’s lymphoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2007;18(Suppl 2):ii55–ii56

Prophylaxis of brain and spinal cord in diffuse large B- cell lymphoma (DLBCL)

M Levin, MD — Tue, 28 Aug 2012 17:29:28 +0000

Brain and spinal cord(CNS) are “sanctuary” sites, places within the body where lymphoma cells can hide out and survive chemotherapy. Testicles is another such site. There remains an open question about whether intermediate risk lymphomas, such as diffuse large cell lymphomas, that invovle organs other than lymph nodes require prophylaxis against CNS involvement alingside methotrexate, that gets well into the CNS form the blood, with follinic acid rescue. The consensus is that some such sites, such as testicular lymphoma, should get prophylaxis and some should not. European Society of Medical Oncology(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 modern chemotehrapy R-CHOP at a tertiary care centre 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.

There is a trial that is looking at this question: Dose Dense Chemotherapy and Rituximab for Young High Risk Diffuse Large B-Cell Lymphoma Patients (CRY-04), NCT01502982

The purpose is to test whether dose densified chemoimmunotherapy followed by central nervous system (CNS) prophylaxis for young high risk diffuse large B-cell lymphoma (DLBCL) patients is feasible and could improve time to treatment failure and reduce the risk of CNS relapses. Six courses of rituximab-cyclophosphamide-doxorubicin-etoposide-vincristine-prednison (R-CHOEP) given in two weeks intervals with the support of G-CSF is followed by one course of high dose methotrexate (HD-MTX) and high dose cytarabine (HD-Ara-C). The results will be compared to a historical Nordic study.

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Adjuvant Therapy for Early-Stage Marginal Zone Lymphoma

M Levin, MD — Fri, 10 Aug 2012 14:10:08 +0000

Extranodal marginal zone lymphoma, also called low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), is a lymphoma that, unlike most other lymphomas, arises outside of lymph nodes, in a number of locations, including the stomach, salivary glands, lung and small intestine. There is evidence for marginal zone lymphoma in general that it might be disseminated at presentation. Therefore, it is tempting to prescribe adjuvant chemotherapy or rituximab after the primary site had been treated to a remission. However that is still an experimental approach.

NCCN on p. NGMLT-2 recommends that extranodal marginal zone lymphoma be treated with observation after resection. If margins are close, as they were in this case, NCCN recommends radiation. It does not recommend adjuvant Rituxan.

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Stem Cell Transplantation for Cutaneous Stem Cell Lymphomas

M Levin, MD — Tue, 19 Jun 2012 17:41:17 +0000

Cutaneous T-cell lymphoma (CTCL) is classified as an indolent hematologic malignancy with distinct clinicopathologic features. Although prognosis varies depending on the stage, patients who have cutaneous tumor, lymph node or visceral involvement, or peripheral blood involvement (Sézary syndrome) generally have a poor outcome.
Evidence for stem cell transplantation, both autologous and allogeneic is on the level of case reports. Experts agree that more investigation is needed.

For advanced disease, systemic treatment options include low-dose methotrexate, photopheresis, biologic response modifiers such as bexarotene capsules, vorinostat (Zolinza), interferons, denileukin diftitox (Ontak), and single-agent chemotherapy. Combination therapies can be used when single agents fail or when patients have advanced or progressive disease. For advanced disease, systemic treatment options include low-dose methotrexate, photopheresis, biologic response modifiers such as bexarotene capsules, vorinostat (Zolinza), interferons, denileukin diftitox (Ontak), and single-agent chemotherapy. Combination therapies can be used when single agents fail or when patients have advanced or progressive disease.

Evidence for stem cell transplantation, both autologous and allogeneic is on the level of case reports. Experts agree that more investigation is needed.

Cutaneous T-cell lymphoma (CTCL) is slowly progressing lymphoma that has unique features. It primarily affects the skin but is also present in the blood and can spread. Although prognosis varies depending on the stage, patients who have skin tumors, lymph node or visceral involvement, or blood involvement (Sézary syndrome) generally have a poorer outcome.

For advanced disease, systemic treatment options include low-dose methotrexate, photopheresis, biologic response modifiers such as bexarotene capsules, vorinostat (Zolinza), interferons, denileukin (Ontak), and single-agent chemotherapy. Combination therapies can be used when single agents fail or when patients have advanced or progressive disease. For advanced disease, systemic treatment options include low-dose methotrexate, photopheresis, biologic response modifiers such as bexarotene capsules, vorinostat (Zolinza), interferons, denileukin diftitox (Ontak), and single-agent chemotherapy. Combination therapies can be used when single agents fail or when patients have advanced or progressive disease.

Evidence for stem cell transplantation, both autologous and allogeneic is on the level of case reports. Experts agree that more investigation is needed before it is widely accepted.

In 2012, the Cochrane team attempted to review available literature evidence to compose a guideline. They found 2077 citations but none were randomized controlled trials. All 41 studies that were thought to be potentially suitable were excluded after full text screening for being non-randomized, not including the condition CTCL or being review articles and not original research. The Cochrane team says in the conclusion section: “We planned to report evidence from genetically or non-genetically randomized controlled trials comparing conventional therapy and allogeneic stem cell transplantation. However, no randomized trials addressing this question were identified. Nevertheless, prospective genetically randomized controlled trials need to be initiated to evaluate the precise role of alloSCT in advanced CTCL.”

The NCCN on p. MFSS-7 does say” “Consider non-ablative allogeneic transplant as appropriate”. A note “aa” says: “The role of allogeneic transplant is controversial. See discussion for further details”. This discussion is found on page MS – 130. It says that allogeneic SCT has been reported in case reports and small series in patients with advanced MF and SS. It references a meta-analysis that compares allogeneic and autologous transplant and concludes that additional study in high-risk patients with advanced diseases is warranted. The rationale for lukewarmly recommending non-ablative approach is probably to reduce toxicity.

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Thalidomide or Lenalidomide and Rituximab for Mantle Cell Lymphoma

M Levin, MD — Tue, 19 Jun 2012 17:35:56 +0000

Thalidomide, lenalidomide and rituximab have no direct effect on MCL cells. However, both indirectly affect peripheral blood mononuclear cell-mediated cytotoxicity, and rituximab induces both complement-dependent and antibody-dependent cellular cytotoxicity (ADCC) against MCL cells. Rituximab-induced ADCC is enhanced by lenalidomide and thalidomide. In a 2004 series, thirteen patients of sixteen enrolled (81%) experienced an objective response, with 5 complete responders (31%). Median progression-free survival (PFS) was 20.4 months (95% confidence interval [CI], 17.3-23.6 months), and estimated 3-year survival was 75%. In patients achieving a complete response, PFS after rituximab plus thalidomide was longer than PFS after the preceding chemotherapy. Severe adverse events included 2 thromboembolic events and 1 grade IV neutropenia associated with thalidomide.Several similar studies show promise, but the combination of rituximab and thalidomide still requires investigation and is not currently recommended by any guidelines.

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