The Virtual Congress on

Lymphoma, Myeloma

and Leukemia

Hairy Cell Leukemia variant (HCL-V) is defined as a rare and indolent form of small, mature, B-cell leukemia characterized by a splenomegaly, an elevated white blood cell (WBC) count and hyper-cellular bone marrow. HCL-V is not considered to be biologically related to classical HCL (HCL-C). The WHO classification included HCL-V as a provisional entity among the unclassifiable splenic B-cell leukaemia/lymphoma together with splenic diffuse red pulp small B cell lymphoma (SDRPL). HCL-V constitutes 0.4% of all lymphoid malignancies and incidence rate is 0.2. In comparison to HCL-C, patients with an HCL-V are often older, present with lymphocytosis, and are resistant to common treatments using purine nucleoside analogs. Morphologically, HCL-V cells are similar to HCL-C but with higher nuclear cytoplasmic ratios and no ribosome-lamella complexes. HCL-V cells   express   bright CD20, bright CD22, CD11c and CD103, but absent CD25 and dim to absent CD123. In addition HCL-V cells do not demonstrate reactivity to tartrate–resistant acid phosphatase (TRAP) and BRAF mutation is absent. Differential diagnosis includes splenic lymphoma with villous lymphocytes (SLVL), SRPL, HCL-C, mantle-cell lymphoma and B-cell prolymphocytic leukaemia (B-PLL). The median survival is approximately nine years, with only 15% survival over 15 years.  Treatment options include splenectomy, purine nucleoside analogs interferon-a, monoclonal antibodies and moxetumomab pasudotox. The results of cladribine monotherapy in HCL-V are inferior to those achieved with cladribine in HCL-C. Rituximab combined with cladribine is more effective than cladribine alone or rituximab alone. Novel agents like ibrutinib are also considered for the treatment of this disease. In addition autologous and allogenic hematopoietic stem cell transplantation can be taken into account in relapsed/refactory cases.

T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with a heterogeneous clinical course, but poor overall survival (OS). In 2018 the T-PLL International Study group (TPLL-ISG) set out to define standardized criteria for diagnosis, treatment indication, and evaluation of response. These criteria were published in Blood in 2019. They will facilitate the design and conduct of clinical trials in T-PLL, which are necessary for the approval of new therapeutics by healthcare authorities. In addition they will provide a useful resource for clinicians treating this rare disease.

In 2019 we also reviewed results from 174 T-PLL patients who were diagnosed or treated at RMH between 1989-2019. This data was presented at the ASH meeting in December 2019. Mean age at diagnosis was 61 years old (range 32-88) and M: F ratio was ~2:1 (113:61). At diagnosis the median white blood cell count was 74 x 10⁹/L (range 10-918), median haemoglobin 126 g/L (range 59-175) and median platelet count 116 x 10⁹/L (range 7-513). Sufficient immunophenotyping data was available for analysis in 135/174 patients. The results showed predictably high expression of CD2, CD3, CD5, CD7, CD52 and TCRαβ. CD25 was positive in 67/135 (50%) of cases, which is higher than the 18-35% seen in the current literature. CD4+/CD8- cases comprised 83/135 (61%) with CD4-/CD8+ 19/135 (14%), CD4+/CD8+ 32/135 (23%) and CD4-/CD8- 2/135 (2%). We analysed OS by decade of diagnosis covering 3 decades 1990-1999, 2000-2009 and 2010-2019. The median OS for the whole cohort was 20.6 months with median OS of 21 months, 23 months and 19 months for each decade respectively. There was no statistically significant difference between the curves by log-rank analysis.

Alemtuzumab was used in 116 patients, 69/116 (59%) receiving it as frontline treatment and 47/116 (41%) as salvage therapy. In 50/116 (43%) alemtuzumab was used as single agent, the remaining 66/116 (57%) receiving combination therapy, mostly pentostatin.

Mean time from diagnosis to receiving alemtuzumab was 6.8 months (range 0-53 months). Overall response rate (ORR) to alemtuzumab was 94/116 (81%) with complete remission (CR) 69/116 (59%), partial remission (PR) 25/116 (22%) and no response (NR) 20/116 (17%). Alemtuzumab produced better response rates when used as intravenous frontline therapy.

Allogeneic stem cell transplant (allo-SCT) was performed in 34 patients. Relapse rate post allo-SCT was 47%, non-relapse mortality 38% and transplant related mortality 29%. Although relapse rates are high post allo-SCT there is a small cohort of patients who are achieving long-term remission.

Our data shows that outcomes in T-PLL have remained unchanged since the first decade of alemtuzumab usage, with no improvement in OS in the last 20 years. Despite improvements in diagnostic techniques and supportive care median OS is static at approximately 20 months. Notably, in the last decade in particular, referrals to our centre have included a higher proportion of patients with relapsed or refractory disease and this may be contributing to the lack of improved survival in our cohort. Nevertheless, these results highlight the need for novel therapies in T-PLL. Given the rarity of T-PLL, international, multicentre, randomised trials such as the ibrutinib and venetoclax trial are needed to improve outcomes.

An outbreak of SARS-CoV-2, which first emerged in Wuhan in December 2019 and rapidly spread within China and to other countries, made the WHO declare the novel infectious disease COVID-19, caused by SARS-CoV-2, a global pandemic.

As hematologists and hemato-oncologist we are interested to know which are the special challenges that COVID-19 poses on Hem-Onc patients and healthcare providers.

First, Hem-onc patients are at particular risk for severe disease related to COVID-19 viral pneumonia. Second, healthcare resources are limited during the pandemic. Third, special measures to minimize patients’ exposure to COVID-19 are necessary. Thus, efforts should be done to minimize patients’ time in clinical areas. And last but not least, specific decisions regarding therapy of hematological malignancies need to be individualized based on disease risk, the risks of immunosuppression, the rates of transmission of COVID-19 and availability of local healthcare resources.

As a general rule,  treatment options with a clear established benefit in terms of survival outcomes should not be postponed for example in acute leukemias and aggressive lymphomas while in the setting of low grade lymphomas, CLL or low risk myeloma, treatment should be omitted or deferred with curtailment of treatment as much as possible. At the same time patients’ time spent in clinical settings should be reduced by using telemedicine /telehealth as much as possible and by changing IV medications to SC or PO.

In the event of infection with COVID-19 in immunocompromised patients the treatment algorithm should be adapted and decisions regarding the approach to the COVID-19 infection should be taken according to the patient’s immune status and the severity of the infection.

In the event of infection with COVID-19 during chemotherapy, chemotherapy should be continued on a case-by-case basis.

Until a few years ago, we did not realize that a quarter of patients diagnosed with Chronic Lymphocytic Leukemia (CLL) were suffering from infections, and 10% of those even dying within 30 days of infections, prior to any CLL specific treatment. Based on an extensive multidimensional time series of health data through Danish National Health Registries, we have created proof of concept that it is possible to predict risk of infections for patients with CLL. Addressing the necessity of developing models that are usable in the clinic, a modelling approach that is able to make predictions for all patients (irrespective of missing data) and providing uncertainty estimates as well as personalized risk factors for each patient prediction is emphasized. CLL-TIM (Treatment Infection Model) is now being prospectively tested to assign patients for the investigator-initiated, international PreVent-ACall clinical trial (NCT03868722), where we are aiming to improve immune dysfunction for patients with CLL by 12 weeks treatment with acalabrutinib and venetoclax. Going forward, we encourage collaborations on developing predictive models that can be applied at different time points of the CLL disease course, allowing testing of various interventions including immunoglobulin substitution, prophylactic antibiotics and novel targeted treatment approaches to improve the immune dysfunction in CLL and to improve the outcome for patients with CLL.

While minimal residual disease (MRD) analysis was commonly accepted as a surrogate marker for progression-free survival (PFS) in the era of immunochemotherapy (ITT) in chronic lymphocytic leukemia (CLL), the advent of kinase inhibitors such as ibrutinib initially questioned its value. More recently, the development of venetoclax, the first inhibitor of bcl2, as well as the prospect of new combinations put back on the spotlight the interest of the analysis of the MRD, not only to evaluate the effectiveness of these associations, but perhaps also to guide the therapeutic strategy.

In this talk, I will address the following potential roles for MRD measurement in CLL:

• Assess response and predict outcome for clinic patients
• Determine duration of treatment for clinic patients
• Monitor patients in remission after treatment
• Improve drug development in clinical trials

Waldenström’s macroglobulinemia (WM), also defined as lymphoplasmacytic lymphoma (LPL), is a rare, distinct indolent lymphoma with an IgM monoclonal gammopathy. Clinical presentation of WM is variable and may be governed by either lymphoplasmacytes infiltration or the IgM monoclone, often related to its immune attributes. Differential diagnosis from other indolent lymphomas and correctly identifying symptoms etiology can be challenging.
With current knowledge of disease pathobiology, we can distinguish between disease patterns according to MYD88 and CXCR4 mutations. These are also important in prediction of disease response and thus, choice of therapy.
Fortunately, there is a variety of approved therapeutic option in previously untreated WM patients, based on either an alkylating agent, proteasome inhibitor, bendamustine, rituximab-alone, or ibrutinib. Therefore, choosing the best regimen depends not only on response rate and PFS, but also on disease presentation, and patient comorbidities and preferences.
In this talk, I will discuss current chemo-immunotherapeutic (CIT) regimens versus ibrutinib treatment, as well as second generation BTK-inhibitors. I will also present new data coming from ASH 2020, portraying future directions in the treatment of WM.

PTCL (Peripheral T cell Lymphoma) represent approximately less than 10% of all NHL in the Western world. The most common entities include: PTCL-NOS, angioimmunoblastic T cell lymphoma (AITL) including the new entity of PTCL with follicular helper phenotype, and anaplastic large cell lymphoma (ALCL) ALK positive and negative.

Despite progress during the last years, there is currently no accepted standard of care for newly diagnosed patients with PTCL. CHOP like treatment and consolidation with autoSCT is the common practice.

In the talk, we will discuss the 1^st line treatment for ALCL and other nodal PTCL including the recent studies. We will discuss the role of autoSCT in 1^st remission, for and against, and targeted therapy in relapse and refractory PTCL.

Marginal Zone Lymphoma (MZL) represents 10 -11% of all B-cell non-Hodgkin lymphomas. Three subtypes are recognized in the World Health Organization classification:  extranodal MZL (EMZL) (7-8%), splenic MZL (SMZL) (2%) and nodal MZL (NMZL) (1.5-1.8%).  MZLs typically exhibit and indolent course with longer survival in patients with EMZL compared than those with SMZL and NMZL. In this presentation we will focus on the treatment of EMZL. There is only one randomized trial in EMZL in rituximab era (IELSG-19). Given the paucity of trial data, treatment policies have been based on large institutional experiences, which in turn have been transformed into guidelines by organizations such as National Cancer Center Network (NCCN) and the European Society of Medical Oncology (ESMO).

In this presentation we will discuss treatments of newly diagnosed EMZL presenting with limited stage and disseminated disease. We will assess risk of high grade of transformation and treatment algorithm in these patients. Finally, we will summarize some of the new data presented at ASH 2020 meeting on treatment of relapsed MZL.

The medical profession today is in the midst of a revolution that is changing the face of medicine. This revolution affects every physician, whether they be residents or senior physicians, young or experienced. Among the factors driving this change are; a fast-evolving world of technology that changes the face of the medical profession, heavy regulation, the new Y and Z generations, patients who become more sophisticated and knowledgeable, and a steadily increasing life expectancy, accompanied by rising health care costs. These changes have a significant impact on every aspect of the doctor’s work.

In a world that is changing ever so quickly and becoming ever more complicated, there is no doubt that any physician who wishes to continue to provide each patient with personalized, compassionate, innovative, professional, and high-quality treatment will need to “upskill” themselves and develop a new mindset and set of skills.

The 5-Lands Model is an inclusive conceptual framework for the skills of the New Era of Medicine. This Model is based on cutting-edge theories on the brain’s plasticity, the future of medicine, and leadership in the age of VUCA (Volatility, Uncertainty, Ambiguity, and Complexity). It is also based on interviews with hundreds of hospital CEOs and medical leaders, L&D leaders, and professors from various universities and faculties (including medical faculties), as well as on the writer’s own experience in implementing upskilling and strategic change management processes in multiple healthcare systems and countries.