On June 20th 2015 in Lugano, Switzerland, a multidisciplinary panel of 25 leading experts met at the European Society of Medical Oncology (ESMO) consensus conference on mature B-cell lymphomas and Chronic Lymphocytic Leukemia (CLL). The panel suggested and voted on recommendations in important subjects that are difficult to consider and include in detail within the ESMO Clinical Practice Guidelines (CPGs). These subjects were: elderly patients, prognostic factors suitable for clinical use, and the ‘ultra-high-risk’ group.
In an article1 published in Annals of Oncology in August 2016 by M. Ladetto of the Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy, and colleagues, the recommendations for the second subject (prognostic factors suitable for clinical use) were reported and focused on four areas of interest:
- Interim PET (Front-Runner Entities [FREs] – HL, DLBCL)
- TP53 mutations and deletions (FRE – CLL)
- COO determination by GEP or IHC (FRE – DLBCL)
- Molecular-based MRD evaluation (FREs – MCL, FL, CLL)
The level or evidence and strength of each recommendation were noted, which were defined based on the ‘Infectious Diseases Society of America-United States Public Health Service Grading System’.2 Below are the recommendations for DLBCL which scored IA and IB (I = Evidence from at least one large randomized, controlled trial of good methodological quality [low potential for bias] or meta-analyses of well-conducted randomized trials without heterogeneity; A = Strong evidence for efficacy with a substantial clinical benefit, strongly recommended; B =Strong or moderate evidence for efficacy but with a limited clinical benefit, generally recommended).
One recommendation for DLBCL was scored IA and fell into the ‘potential role of COO determination by IHC or GEP as a prognostic tool’ category.
- The panel strongly encourages the use of GEP in prospective clinical trials for prognostication
One recommendation was scored IB, which also fell into the ‘potential role of COO determination by IHC or GEP as a prognostic tool’ category.
- Clinical trials of interventions based on GEP results are encouraged
The panel discussed in detail GEP and IHC, comparing the two and identifying their strengths and limitations:
- GEP technologies are currently limited to very specialized laboratories; GEP may become more widely available and applicable via the introduction of more user-friendly technologies
- IHC compared to GEP has major reproducibility issues; GEP using well-established high-throughput commercial chips is robust, but inter-laboratory variability requires investigation
- The reporting system for IHC has been standardized, however the algorithms have limitations; the panel also raised substantial concerns regarding IHC’s prognostic value
- No standardized system for data interpretation or result reporting is available for GEP
- These deliberations are especially important in regards to drugs which potentially have different activity in GCB versus ABC DLBCLs
The panel advise that these additional recommendations should be read in conjunction with the already-published ESMO CPGs for the diagnosis, treatment and follow-up of DLBCL.
The European Society for Medical Oncology (ESMO) consensus conference on mature B-cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommendations on critical subjects difficult to consider in detail in the ESMO Clinical Practice Guidelines. The following areas were identified: (i) the elderly patient, (ii) prognostic factors suitable for clinical use and (iii) the 'ultra-high-risk' group. Before the conference, the expert panel was divided into three working groups; each group focused on one of these areas in order to address four clinically relevant questions relating to that topic. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, each working group developed recommendations to address each of the four questions assigned to their group. These recommendations were then presented to the entire panel and a consensus was reached. This manuscript presents recommendations dedicated to the second area of interest, i.e. prognostic factors suitable for clinical use. The four topics [i.e. interim positron emission tomography (PET), TP53 mutations, cell of origin (COO) and minimal residual disease (MRD)] were primarily chosen because of the bulk of available data together with the lack of clear guidance regarding their use in clinical practice and within clinical trials. Results, including a summary of evidence supporting each recommendation, are detailed in this manuscript. The panel acknowledged that detection of TP53 inactivation by deletion or mutation in CLL should be implemented in clinical practice (level of evidence I, strength of recommendation A). Due to their potentially high prognostic value, at least in some lymphoma entities, implementation of interim PET, COO and MRD was highly recommended in the context of clinical trials. All expert panel members approved this final article.
- Ladetto M. et al. ESMO Consensus Conference on Malignant Lymphoma: General Perspectives and Recommendations for Prognostic Tools in Mature B-Cell Lymphomas and Chronic Lymphocytic Leukaemia. Ann Oncol. 2016 Oct 4. pii: mdw419. [Epub ahead of print].
- Dykewicz C.A. Summary of the Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis. 2001; 33(2):139–144. doi: 10.1086/321805.