JSM: Welcome. We are here for ecancer.tv at the Haematology Debate 2015 in Barcelona. It is my pleasure to introduce four prestigious colleagues that are going to share with you the most relevant findings that we have been discussing over these two days on lymphoma, including mantle cell lymphoma, CLL and multiple myeloma. Please, Professor Tim Illidge, would you mind just to start with the lymphoma?
TI: Thank you. Our workshop has been about diffuse large B-cell lymphoma and we are edging forward in the treatment of large B-cell lymphoma to the next big breakthrough after the addition of rituximab to CHOP chemotherapy. What we have looked at is the response adjusted therapy and the two recent trials, both from the German and the Canadian groups, have demonstrated that PET is extremely good at predicting outcome but we cannot switch therapy according to the PET response. We’ve also looked at a range of different new drugs and the phase II studies are provocative and suggest that we may in the next few years see improvements in outcome with a more personalised approach towards the treatment of large B-cell lymphoma. Particularly exciting candidates are the ongoing trial from the NCRI SAC group with bortezomib with ibritumomab and also with lenalidomide, the so-called R-Squared therapy. Finally, the data that emerged this year with the use of radiotherapy in the treatment of bulk disease is also really rather provocative and suggests that radiotherapy for some patients with diffuse large B-cell lymphoma is back in the game, suggesting that radiotherapy should be given to patients that have bulky disease around 7.5cm and greater. What we don’t know and a source of ongoing investigation will be to see whether radiotherapy provides the same benefit for those patients that have bulk disease where the bulk goes and they become PET negative. So that remains the basis of an ongoing trial that we will do to randomise patients who are PET negative at the end of treatment to see whether they still derive the same benefit for radiotherapy to their bulk disease.
JSM: OK, thanks very much for this excellent summary. Now Umberto Vitolo from Torino, Italy. Mantle cell lymphoma.
UV: Mantle cell lymphoma is a rare disease but is a challenging disease because of course the prognosis of these patients so far is not as good as in other types of lymphoma. We have very good news for the patients now that we have a variety of newer drugs that are very effective in mantle cell lymphoma. In the workshop and the plenary session that we had yesterday we discussed some new evidence in mantle cell lymphoma, first for the young patient the issue of the efficacy of rituximab maintenance after autologous stem cell transplant that has been recently demonstrated by the French group. There is an advantage to give rituximab maintenance even after autologous stem cell transplant in order to reduce the relapse rate as this is a safe treatment without any big complications. But the second point that we discussed as a possibility, at least for a subgroup of patients in mantle cell lymphoma, that we can give now chemotherapy free regimens with the association of different drugs. So there are interesting data with R-Squared regimens, that means rituximab plus lenalidomide, that was presented at ASH. With this simple regimen the overall response rate is about more than 80% with a prolonged progression free survival. Also in the relapsed setting we discussed the use of different drugs like BTK inhibitors, like ibrutinib, that we already know the efficacy in mantle cell lymphoma. The big point for maybe the first one is that ibrutinib can be safely combined with other drugs like rituximab, Dr [?] presented a combination for the first time with rituximab. This seems to improve the efficacy of ibrutinib when compared with ibrutinib single agent; it’s not a randomised study but just a phase II study. Also was presented lenalidomide in single agent that was more effective than any single agent chemotherapy in a randomised fashion. The key point now is just to find out what is the best patient for each type of novel drug. We may have a patient that will be more sensitive to ibrutinib, another one more sensitive to lenalidomide. There are some ongoing studies based on molecular studies, molecular findings. We try to find out which is the best drug for each patient. There are some preliminary data that suggests, for instance, that some mutational pathway could lead to a resistance to ibrutinib or to other types of drugs. So this probably is our goal in the future, just to find out who are the resistant patients to the newer drugs.
JSM: Thank you very much indeed. Now CLL, Francesc Bosch from Barcelona, where we are, in Spain please?
FB: Thank you, thank you Jesus. So we are in an interesting and new era in CLL. In this era we are covering the gap between biology and science and the therapy. In this new field, the new era, we have two big players which are ibrutinib and idelalisib. These new players are covering an unmet need like high risk CLL, like treatment of relapsed patients. So with these new drugs we are able to treat and obtain high response rates in these patients with no effective therapy so far. So, in this new era we have new data that has been presented in the last meetings, data that are consolidating the concept of the activity of these drugs, alone or in combination with monoclonal antibodies. So this is an exciting time for CLL, very exciting, because we are challenging the way we are looking at this disease. So we are challenging the concept of response because with these new drugs, very effective drugs, patients are controlling the disease but they don’t have a full complete response. We are challenging the possibility of transplanting those patients, that was an alternative of therapy, and now using ibrutinib or idelalisib probably we don’t need to do allogenic transplant any more.
JSM: Thank you very much. And now it is my pleasure just to close this session by discussing multiple myeloma. There are emerging data about the possibility of treating elderly patients and the possibility of using together two standards of care, bortezomib melphalan prednisone with lenalidomide either in a sequential or in an alternative way. The Spanish group has shown that with this double scheme you can reach approximately three years progression free survival, particularly in patients less than 75 years of age. This is good news. Regarding the transplant candidate patients the debate is early versus late transplant. Ongoing studies but at the last ASH meeting preliminary data was presented by the Italian group showing that early transplant is apparently superior to a delayed transplant, mainly because some of the patients that postponed the transplant from the time of relapse are not able to receive such a transplant. Also there is an important debate about the duration of maintenance; maintenance with lenalidomide or bortezomib or both together or the new drugs is showing benefit but we don’t know for how long and whether or not they should be offered also to patients that are CR or minimal residual disease negative. Regarding the relapsed patients the most attractive information now is coming from the new monoclonal antibodies, particularly the CD38 monoclonal antibodies that have shown efficacy as single agent and even higher efficacy in combination. In fact, they are being also tested in the newly diagnosed patients. Finally it was presented at the last ASH meeting and has been recently published in Blood also in the relapsed setting a large randomised trial comparing one of the standards of care, lenalidomide dex, versus the same plus carfilzomib. The triplet in the relapsed setting is showing impressive results with benefit in PFS and overall survival. Then it’s a continuous improvement for myeloma patients and this is very good news for all of us. It is now my time just to close the session by thanking all of you for joining us. Thank you very much.
