The survival rate of multiple myeloma (MM) patients has drastically increased recently as a result of the wide treatment options now available. Younger patients truly benefit from these innovations as they can support more intensive treatment, such as autologous stem cell transplant or multiple drug association (triplet, quadruplet). The emergence of immunotherapy allowed new combinations principally based on monoclonal anti-CD38 antibodies for these patients. Still, the optimal induction treatment has not been found yet. While consolidation is still debated, maintenance treatment is now well acknowledged to prolong survival. Lenalidomide monotherapy is the only drug approved in that setting, but many innovations are expected. Older patients, now logically named not transplant-eligible, also took advantage of these breakthrough innovations as most of the recent drugs have a more acceptable safety profile than previous cytotoxic agents. For this heterogenous subgroup, geriatric assessment has become an essential tool to identify frail patients and provide tailored strategies. At relapse, options are now numerous, especially for patients who were not treated with lenalidomide, or not refractory at least. Concerning lenalidomide refractory patients, approved combinations are lacking, but many trials are ongoing to fill that space. Moreover, innovative therapeutics are increasingly being developed with modern immunotherapy, such as chimeric antigen receptor T-cells (CAR-T cells), bispecific antibodies, or antibody–drug conjugates. For now, these treatments are usually reserved to heavily pre-treated patients with a poor outcome. MM drug classes have tremendously extended from historical alkylating agents to current dominant associations with proteasome inhibitors, immunomodulatory agents, and monoclonal anti-CD38/anti SLAMF7 antibodies. Plus, in only a couple of years, several new classes will enter the MM armamentarium, such as cereblon E3 ligase modulators (CELMoDs), selective inhibitors of nuclear export, and peptide–drug conjugates. Among the questions that will need to be answered in the years to come is the position of these new treatments in the therapeutic strategy, as well as the role of minimal residual disease-driven strategies which will be a key issue to elucidate. Through this review, we chose to enumerate and comment on the most recent advances in MM therapeutics which have undergone major transformations over the past decade.

As the global population is aging and survival in multiple myeloma (MM) is increasing, treating older MM patients, redefined as non-transplant eligible (NTE), is becoming more frequent. Yet, treating these patients remains a real challenge especially because of a marked heterogeneity in the population and an increased susceptibility to treatment toxicity. Indeed, the balance between efficacy and safety must be considered at all time throughout the treatment history for these patients. Therefore, younger and older patients were historically treated in a very different way, even though the safety profile of most anti-myeloma drugs has drastically improved over the years. The emergence of immunotherapy (IT) has largely widened the therapeutic options available in MM and above all has allowed a therapy at optimal dose, and therefore optimal activity, for all patients independently of their frailty features, with no increase in safety issues. Among the novel anti-myeloma IT-based agents, anti-CD38 monoclonal antibodies (mAbs) are now becoming the new backbone of treatment for NTE patients, in association with lenalidomide and dexamethasone. Moreover, several new IT-based drugs are currently being developed and investigated either alone or in association; such as new anti-CD38 mAbs, anti-CD38 mAbs with many different combinations, but also the CART cells, bispecific T-cell engager (BiTEs), or antibody drug conjugate (ADC) targeting BCMA. One would expect that immunotherapy will ultimately change and even transform the MM landscape, even for elderly patients. Immunotherapy represents a shift in treatment paradigm in MM as it provides truly efficient drugs with a very favorable safety profile.

Bone lesions are rarely reported in Hairy Cell Leukemia (HCL). We report two BRAFV600E mutated HCL patients presented bone lesions at foreground, poor bone marrow involvement and the important role 18F-FDG PET/CT played in their management. We discuss the crucial role that 18F-FDG PET/CT could play in HCL routine practice.

Background. Acute myeloid leukemia (AML) incidence increases with age, but elderly patients are often too frail to receive intensive chemotherapy (IC). Instead, treatment with hypomethylating agents (HMAs) is usually proposed, even if they have not demonstrated any real improvement over best supportive care. However, clinical practice has shown a significant difference in overall survival (OS) between responding and non-responding patients to HMAs. Thus, we aimed to assess predictive criteria of HMA response in elderly and frail AML patients. We reviewed the literature for any existing scores: none was found for elderly unfit patients. On the other hand, 3 models/scores existed for fit elderly patients undergoing IC : in the ALFA 9803 trail published by Malfuson and al, the HOCSG model in the MRC AML11 and LRF AML trails by Wheatley and al and finally the MDACC model by Kantarijan and al. Methods. We reviewed all patients aged ≥ 60 years old (y.o) diagnosed with AML, unfit for IC and treated with Azacytidine (AZA) alone in first line from July 2015 to December 2019 in Poitiers' University Hospital. The ineligibility to IC was defined by an age > 75 y.o and/or the appreciation by the physician based on performance status (ECOG) and the evaluation of comorbidities with Charlson Comorbidity Index (CCI). The type of AML (de novo versus secondary) and the 2017 ELN prognosis score were also assessed. Results. Among 63 patients recruited, 86% were older than 70 y.o and 29% older than 80. Frailty criteria were found with a ECOG ≥ 2 in 11 (17%) and a CCI ≥ 3 in 29 (45%) patients. Secondary AML was found in 41 (63%) of patients. Adverse karyotype was detected in 21 (32%) patients and 2017 ELN score was quoted as adverse in 25 (38%) patients. After a median follow up of 10.75 months (IQR 3.98 - 17.94) for the whole cohort, median OS was 10.75 months (95%CI 6.37476 - 14.984). Among 54 (86%) evaluable patients, 50 reached some response: at least hematological improvement according to 2003 International Working Group criteria in 20 of them (37%), and stable disease in 30 (55.6%) patients. Patients reaching at least hematological improvement were able to complete a median of 11.5 cycles (IQR 7.5 - 17) vs 6.5 cycles (IQR 3 - 12). Sadly 23 (35%) patients died before achieving 6 cycles. In our cohort the 2017 ELN score failed to predict risk assessment in elderly frail patients. The ALFA model and HOCSG score were also not able to identify treatable patients neither to predict mortality in our cohort. Interestingly the MDACC high-risk category was able to identify the patients who would not benefit from AZA treatment with worst survival rates (HR 3.01; 95%CI 1.04 - 8.79). Conclusion. To date, stratification scores were developed for young fit patients, undergoing IC. Those scores predict poorly response to HMA and OS in unfit patients. In the era of new treatments and combinations with AZA, there is an urgent and growing need for dedicated prognosis model for unfit elderly AML patients. Disclosures Leleu: Bristol-Myers Squibb: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Gilead Sciences: Honoraria; Celgene: Honoraria; Janssen-Cilag: Honoraria; Karyopharm Therapeutics: Honoraria; Merck: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Oncopeptides: Honoraria; Pierre Fabre: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Other: Non-financial support.