Hematology

MCL is an aggressive B cell malignancy which is incurable with standard therapies. In this video, the current standard of care (SOC) for mantle cell lymphoma (MCL), including not only the established therapies but also the emerging therapies that will impact the management of MCL in the future, is discussed. Dose intensification is the current SOC. It will be important to identify how best to integrate the new molecular approaches into this regimen in order to provide a multimodal approach. Data from the MERGE study and broader lymphoma studies, using lenalidomide (standard dose of 25 mg oral once daily) have been presented at this year’s EHA and show promising results. However, side effects can be an issue, which can be managed in part through a reduction in the dose. Ibrutinib, an oral inhibitor of the Bruton's tyrosine kinase in the B cell receptor pathway, has shown impressive response rates in heavily pre-treated patients, and has been associated with an acceptable side effect profile. Another interesting experimental drug is ABT-199, a potent and selective BCL-2 inhibitor. It has shown some interesting preliminary results in patients with MCL. The challenge in the future will be to determine which treatment is appropriate for which patient types, at which stage of the disease and for how long it should be used.

Treating elderly MM patients is challenging because of the heterogeneity of this patient population. This needs to be taken into consideration when choosing treatments. Full dose ASCT can be considered in patients

In patients with biochemical relapse with a small increase in M protein levels in the serum or urine, treatment is not initiated immediately. In patients with a steep increase in M protein levels, a doubling or presentation of symptoms, treatment should be initiated. Re-treatment with bortezomib and lenalidomide is a possible option in the relapsed patient, particularly if the relapse is more than 2 years since treatment was given. In a clinically relapsed patient or in those who relapse occurs within 2 years, a new treatment regimen from that first used should be considered. For patients refractory to bortezomib or lenalidomide, new proteasome inhibitors and immunomodulatory drugs are available, including carfilzomib and pomalidomide. These may provide alternative treatment options and change the outcome of relapsed MM patients in the future.

Induction regimen for transplant eligible multiple myeloma (MM) patients is 4-6 course of a triple drug regimen, typically with bortezomib, dexamethasone and cyclophosphamide (VCD), followed by ASCT. In some centres the alkylating agent may be substituted with thalidomide (VTD) or lenalidomide. Important factors determining which treatment to consider include effectiveness, tolerability and availability for first-line use. The use of consolidation after ASCT may provide additional benefit, but this is still to be confirmed. It is being investigated in a number of trials, but Phase III data are needed and it is not routinely used outside of a clinical trial. Maintenance with thalidomide has demonstrated improvements in progression free survival (PFS) and overall survival (OS). Lenalidomide has also demonstrated a significant PFS benefit, but not OS benefit. Maintenance is seen as an attractive treatment option for transplant MM candidates but is still confined to use in the clinical trial setting. Delaying transplant may be a viable option for some patients. However, the recommendation is that all eligible patients should be offered ASCT.

Multiple myeloma (MM) is the second most common haematological cancer. There is no cure and the 5-year relative survival rate is around 40%. There is, therefore an urgent need to develop new treatment in order to improve survival. The benefits of bortezomib, thalidomide and dexamethasone (VTD) as induction therapy prior to autologous stem cell transplantation (ASCT) in newly diagnosed young patients has been demonstrated in Phase 3 studies. Consolidation therapy is used in many centres across Europe, the US and Canada. Phase 3 data has been published supporting bortezomib as a single agent consolidation therapy. There are several ongoing studies investigating lenalidomide-combination therapies in early phase of treatment of MM. Consolidation therapy increases the rate of high quality responses, which translates to prolonged progression free survival. More data is needed to support the use of maintenance therapy in MM. There is strong data to support the use of VTD as consolidation therapy. The management of relapsed MM is a particular challenge, which is often addressed through the use of ASCT. Pomalidomide and carfilzomib are two additional agents that are being investigated in MM, with carfilzomib expected to receive approval later this year.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in Europe. It is most frequently diagnosed in elderly patients and many patients present with comorbidities, both of which impact on the use of aggressive standard treatments. Targeted therapies can be utilised effectively in patients with CLL and could be used to minimise the side effects of chemotherapy. In a cohort of 250 CLL patients treated with ibrutinib, 150 received therapy for over 1 year. Within this group of patients only 20 patients stopped responding to therapy, including 5 patients who developed mutations that led to resistance. Ibrutinib has also been investigated in combination with bendamustine and rituximab in relapsed or refractory patients. In the CLL11 trial, GA101 plus chlorambucil, rituximab plus chlorambucil and chlorambucil alone were compared in elderly patients with comorbidities. Addition of GA101 or rituximab to chlorambucil both significantly increased PFS versus chlorambucil alone. However, large number of patients with GA101 had Grade 3 and 4 infusion toxicities, mostly in the first couple of infusions. Data on another experimental treatment, CC-292, was presented. It has been found to be generally well tolerated and was associated with significant nodal reduction and partial responses in heavily pre-treated CLL patients. Understanding the clonal heterogeneity of CLL will likely impact on the management of this disease in the future.

Prof Jesus San Miguel talks with ecancer at the 18th EHA Congress about the MM-003 trial. MM-003 is a large, multi-centre phase III study that assessed the efficacy and safety of a new drug, pomalidomide (POM) in combination with low-dose dexamethasone (POM LoDex) and compared this combination with high dose dexamethasone in MM patients with late stage disease which have previously failed lenalidomide and bortezomib.

Prof Philippe Moreau talks to ecancer at the 18th EHA Congress about the results of a phase I/II trial that tested carfilzomib plus melphalanprednisone in elderly patients with newly diagnosed multiple myeloma.