ASH 2019

This meeting is the premier and largest annual international haematology conference that was attended by over 30,000 experts in haematology.
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Lymphoma Australia was successful in receiving a global grant from AbbVie to conduct interviews with Australian and international experts in lymphoma and chronic lymphocytic leukaemia (CLL). The interviews will report the latest information about lymphoma/CLL clinical trials and studies from around the world and were presented during the ASH meeting. These interviews will be shared around the world through patient advocacy groups.

Lymphoma Australia conducted almost 40 interviews during the 4 days of the meeting and we would like to extend a heartfelt thank you from the lymphoma / CLL community to everyone who shared their time, knowledge and expertise with us.

B-cell Lymphoma

Dr Laurie Sehn – ASH Lymphoma Updates.
Dr Laurie Sehn from British Columbia Cancer Centre from Vancouver, Canada is Chair of the medical advisory board for the International Lymphoma Coalition. Dr Sehn discussed some of the highlights in novel therapies that were presented during the ASH meeting for lymphoma. These included Polatuzumab (antibody drug conjugate) for diffuse large B-cell lymphoma (DLBCL) and Mosunetuzumab – (bispecific antibody) used for B-cell non-Hodgkin lymphomas.
Dr Chan Cheah – Phase I Study TG-1701 Relapsed or Refractory B-cell Lymphoma.
A/Prof Chan Cheah, Consultant Haematologist, Sir Charles Gairdner Hospital, Hollywood Private Hospital & Blood Cancer Research WA, in Perth, Western Australia, discussed a poster presentation at ASH of a trial that was conducted in Australia using a new generation Bruton’s Tyrosine Kinase (BTK) inhibitor called TG-1701 used in patients with relapsed/refractor B-cell malignancies. This oral medication is given as a single agent in combination with umbralisib (PI3K inhibitor) and ubiltuximab (glycoengineered anti-CD20 monoclonal antibody).
Dr George Follows – Lymphoma Updates.

Dr George Follows is the Lymphoma/CLL Clinical Lead for Cambridge and he also holds a number of appointments including the chair of the UK CLL forum. Dr Follows discussed updates for lymphoma that have been presented during the ASH meeting of interest. These included the phase I trial using a new medicine called Monunetuzumab that is a bispecific monoclonal antibody that targets CD3 and CD20 and has led to durable responses in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including patients who relapsed from CAR T-cell therapy.

Dr Stephen Schuste – Mosunetuzumab induces durable complete remissions in patients with B-cell non-Hodgkin lymphoma.

The bispecific monoclonal antibody Mosunetuzumab, which targets CD3 and CD20, led to durable responses in patients with B-cell non-Hodgkin lymphoma (NHL), even in those who had disease that was relapsed or refractory to chimeric antigen receptor (CAR) T-cell therapy. Dr Schuste discusses the ongoing phase I/Ib study (GO29781; NCT02500407) of mosunetuzumab in patients with B-cell non-Hodgkin lymphoma (NHL), who are relapsed/refractory (R/R) to CAR-T therapies or for whom a delay in effective therapy excludes this approach. Preliminary data support that mosunetuzumab has favorable tolerability and durable efficacy in heavily pre-treated R/R B-cell NHL.

Dr John Leonard – highlights from the meeting for lymphoma.

Dr Leonard discussed his expert opinions from lymphoma presentations during the meeting. He discussed a number of topics that included: • Follicular lymphoma – chemo free regimens • Diffuse Large B-cell Lymphoma – bone health in patients post R-CHOP and CAR T-cell therapy • Mantle Cell Lymphoma – new medicines in combination with chemotherapy • DNA blood testing • Lymphoma vaccines

Chronic Lymphocytic Leukaemia (CLL) & Small Lymphocytic Leukaemia (SLL)

Dr Brian Koffman – CLL updates & patient advocacy.

Dr. Koffman, a well-known doctor, educator and clinical professor turned CLL patient, has dedicated himself to teaching and helping the CLL community since his diagnosis in 2005. Dr. Koffman believes that his dual status as a physician and patient provides a unique experience and understanding which allows him to provide clear explanations of complex issues and to advocate for his fellow patients and inform his fellow healthcare providers. This is especially important in view of the rapidly changing therapeutic landscape. Dr Koffman is the co-founder of the CLL Society, USA. Dr Koffman discussed the CLL updates from the conference including updates about CAR T-cell therapy, ibrutinib, acalabrutinib, sequencing of medications and different combination therapy. He also discussed best management of CLL, including genetic testing prior to treatment and those patients with unmutated disease, 17p del should not have chemotherapy, rather targeted therapy.

Prof John Gribben and Deborah Sims – Overview of CLL treatment.

Prof Gribben discussed his view of the updates from the meeting where many of the presentations reinforced that the treatments that are being used are good as there have been longer follow up. With a longer follow up also comes the knowledge of new toxicities that may appear. We can then educate patients better with having a better idea of what to expect. He also discussed the new generation novel therapies that have been introduced, not only in CLL, but other lymphomas such as Follicular lymphoma & Mantle cell lymphoma. There are also many early phase clinical trials with new medications that show promise. The next concern is that with these novel therapies and combination therapies, comes an increased expense for the health systems.

Prof Stephan Stilgenbauer and Deborah Sims – Updates on the management of CLL/SLL.

Prof Stilgenbauer provided an overview of the treatment updates for patients with CLL/SLL from the ASH meeting. He discusses the use of novel therapies as single agents and in combinations that are having significant results for patients, especially those who have unmutated disease and therefore do not respond to traditional chemotherapy-based management. Future therapy for CLL/SLL might be that chemotherapy may become a second or a third line treatment.

A/Prof Constantine Tam and Deborah Sims – CLL & Mantle Cell Lymphoma.

A/Prof Constantine Tam, Peter MacCallum Cancer Centre, RMH & St Vincent’s Hospital spoke to Deborah Sims, from Lymphoma Australia. Dr Tam provides his insights from the highlights from the meeting on CLL and Mantle cell lymphoma. He provided an overview of his 3 highly praised presentations for Chronic Lymphocytic Leukaemia (CLL) & Small Lymphocytic Lymphoma (SLL).

Dr George Follows – CLL updates.

Dr George Follows from the UK spoke with Lymphoma Australia at the American Society of Hematology (ASH) meeting recently held in Orlando, USA. Dr Follows is the Lymphoma/CLL Clinical Lead for Cambridge and he also holds a number of appointments including the chair of the UK CLL forum. He discussed the updates on the latest research and study results presented at the ASH meeting on CLL.

Dr Nitin Jain and Deborah Sims – Ibrutinib & Venetoclax in patients with CLL.

Dr Nitan Jain is an Associate Professor in the Department of Leukaemia at the University of Texas MD Anderson Cancer Center in Houston, Texas, USA. Dr Nitan discussed his 2 presentations during the ASH meeting of the 2 studies conducted at MD Anderson Cancer Centre using combined Ibrutinib and venetoclax with patients with chronic lymphocytic leukaemia (CLL) in both first-line treatment and those with relapsed/refractory disease. Results showed that in both groups the combined treatment using ibrutinib and venetoclax is an effective chemotherapy-free oral regimen for patients with CLL and further studies will be ongoing.

Dr Tanya Siddiqi – CAR T-cell in relapsed/refractory CLL.

Dr Tanya Siddiqi is the Director, Chronic Lymphocytic Leukaemia Program, Toni Stephenson Lymphoma Centre and A/Prof Department of Hematology & Hematopoietic Transplantation at the City of Hope National Medical Centre, Duarte, USA. Dr Siddiqi discussed her presentation during the meeting of the phase I study treating relapsed or refractory patients with CLL. All patients had previously received at least 3 standard treatments, including ibrutinib and half of patients had also received venetoclax. The study treated 23 patients with CAR T-cell therapy where over 80% achieved durable responses over 6 months. Follow up continues.

Prof John Seymour – Overview of the Murano study – CLL/SLL.

Prof Seymour presented the four-year analysis of the Murano study that confirms sustained benefit of time limited Venetoclax & rituximab in relapsed or refractory chronic lymphocytic leukaemia (CLL). Venetoclax (Ven) is a highly selective oral inhibitor of key apoptosis regulator BCL-2, which is overexpressed in CLL. MURANO (a randomized Phase III study) compared fixed-duration VenR with standard bendamustine-rituximab (BR) in R/R CLL. The superior progression-free survival (PFS) of VenR versus BR was established in the first pre-planned analysis (Seymour et al. N Engl J Med 2018); continued PFS benefit was seen with longer follow-up and after all patients had completed therapy.

Prof Peter Hillmen – Challenges in the CLL/SLL treatment landscape.

Prof Hillman discusses some of the challenges of the rapidly changing treatment landscape for CLL/SLL with many novel therapies on the market.

Prof Peter Hillmen – CLL updates from ASH 2019.

Prof Hillmen discussed some of the most significant highlights from the meeting on novel therapy trials used in the frontline setting that were presented that showed good results with the use of ibrutinib (BTK inhibitor), acalabrutinib (new generation BTK inhibitor), venetoclax (BCL2 inhibitor) and the use of combination therapies. He also discussed clinical trials in the relapsed setting showing good results that included CAR T-cell therapy. Thank you to Leukaemia Care for sharing the interview with Lymphoma Australia.

Prof Miles Prince – Genetic testing (CLL/SLL) & CAR T-cell therapy.

Prof Prince discussed his opinions of the main topics of interest for lymphoma from the meeting. He discussed that the best way to treat a patient’s lymphoma, their diagnosis needs to be understood and fully known. It has been demonstrated that patients who are diagnosed with CLL/SLL need to have genetic testing prior to receiving treatment. Patients who have unmutated and a TP53 mutated CLL/SLL, chemotherapy has been shown to not be as effective for this patient group. In the USA and the UK (and some European countries) patients are funded to receive Ibrutinib front-line, however this is still not the case in Australia, where patients receive chemo-immunotherapy and ibrutinib in second line treatment.

Diffuse Large B-cell Lymphoma (DLBCL)

A/Prof Chan Cheah – Aggressive Lymphoma, Diffuse Large B Cell lymphomas.

A/Prof Cheah revises the paper “Aggressive Lymphoma (Diffuse Large B-cell and other aggressive b-cell non-Hodgkin lymphomas) – results from prospective clinical trials: optimizing frontline chemotherapy” session held on Sunday 8th December at ASH 2019.

Dr Jason Westin – Diffuse Large B-cell Lymphoma updates & the Smart Start Study.

Dr Westin discussed some of the highlights from the conference in DLBCL including CAR T-cell therapy and updates from studies that use less chemotherapy and therefore improving the toxic side effects for patients

Follicular Lymphoma

Dr Loretta Nastoupil – Follicular lymphoma study – Part 1.

Dr Nastoupil discussing the results of her phase II study of Obintuzumab (type II anti-CD20 monoclonal antibody) and Lenalidamide (immunomodulatory agent) in previously untreated, high tumour burden FL. This combination of therapies was seen to be well tolerated and effective in a previous study for patients treated in relapsed or refractory FL.

Dr Loretta Nastoupil – Follicular lymphoma study – Part 2.

Dr Nastoupil discussed the results of her phase II study of Obintuzumab (type II anti-CD20 monoclonal antibody) and Lenalidamide (immunomodulatory agent) in previously untreated, high tumour burden FL. Further study of this effective, immune therapy approach in untreated FL is warranted. Dr Nastoupil discusses the reasons for this effective and well tolerated approach for any population of patients with Follicular lymphoma.

A/Prof Chan Cheah – Follicular lymphoma clinical trial update.

Dr Cheah discussed a presentation provided by Dr Loretta Nastoupil from MD Anderson Cancer Centre, Texas during the ASH 2019 meeting. The phase II study looked at treating previously untreated Follicular lymphoma patients with Obintuzumab (type II anti-CD20 monoclonal antibody) and Lenalidamide (immunomodulatory agent), with a high tumour burden. This combination of therapies was seen to be well tolerated and effective in a previous study for patients treated in relapsed or refractory FL conducted at MD Anderson Cancer Centre by Prof Nathan Fowler (RELEVANCE study).

Dr Allison Barraclough -Nivolumab + Rituximab in First-line Follicular Lymphoma.

Dr Barraclough discussed the interim results of a first in world phase II study, that is led by Dr Eliza Hawkes, front-line management of patients with stage 1-3A follicular lymphoma. The study uses a combination immune therapy only approach, that had only been previously tried in the relapsed setting. Patients receive nivolumab only for the first 8 weeks and if they achieve a complete response, will continue with single agent nivolumab. For those who only achieved a partial response would go onto having a combination on nivolumab and rituximab. Results were good with on overall response rate (ORR) of 80% and over a half of these patients achieved a complete response (CR). There was a low toxicity profile, where many patients were still able to work and continue normal life activities

Mantle Cell Lymphoma

Dr Sasanka Handunetti – Mantle Cell Lymphoma (Update of the AIM study).

Dr Handunetti discussed her presentation about the three-year update of the phase II AIM study (TAM, et al, NEJM 2018) conducted at Peter MacCallum Cancer Centre in Melbourne, using combination BTK inhibitor ibrutinib and BCL-2 inhibitor venetoclax therapy in patients with poor prognosis mantle cell lymphoma (MCL). Results showed a median progression free survival of 29 months. It raised the question that there is a possibility of limited duration targeted-agent therapy in the management of relapsed or refractory MCL.

Prof Steven Le Gouill – Mantle Cell Lymphoma study.

Prof Le Gouill discussed his phase I study for newly diagnosed MCL using Ibrutinib, Venetoclax and Obintuzumab that have all been previously shown to have efficacy in the relapsed/refractory setting as single agents and in combination in the relapsed/refractory (R/R) MCL. He also provided an overview of standard of care for patients with MCL for the younger patient and the older patient in both the front line and R/R management.

Prof Simon Rule – Mantle Cell Lymphoma Update.

Prof Simon Rule discussed his poster presentation at the meeting looking at a 7.5 year follow up of patients with relapsed or refractory MCL who patients on ibrutinib (BTK inhibitor) that showed a significant number of patients still in remission greater than 5 years. It also showed that the patients who received Ibrutinib in earlier lines of therapy had a better durable response, than those who received it lateistique.

KTE-X19: A CAR T-Cell Option for Mantle Cell Lymphoma?

Ninety-three percent of patients with relapsed/refractory mantle cell lymphoma (MCL) responded to treatment with KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, according to results from the ZUMA-2 trial presented at the 2019 ASH Annual Meeting.

Hodgkin Lymphoma

Dr Jessica Hochberg – Chemotherapy, Young Adults & Hodgkin Lymphoma.

Cure rates for newly diagnosed Hodgkin Lymphoma is high with combined use of chemoradiotherapy. However, this often results in significant adverse physical and psychosocial function that can significantly impact the quality of life among survivors. The addition of Brentuximab vedotin and Rituximab to combination risk adapted chemotherapy (without cyclophosphamide, etoposide or bleomycin) for newly diagnosed Hodgkin Lymphoma appears to be safe in children, adolescents and young adults. Our results show significant promise with a CR rate of 100%, 58% rapid early response and significant reduction in the use of toxic chemotherapy and radiation. The EFS/OS to date is 100% with a median follow up time of greater than 3.5 years.

Prof Andrew Evens – HoLISTIC Hodgkin Lymphoma International Study.

Prof Evens is an active member of the HoLISTIC (Hodgkin Lymphoma International Study for Individual Care) – an international consortium coalescing a team of diverse experts from across the world to study the salient aspects of Hodgkin lymphoma prognosis, epidemiology, treatment, survivorship and health outcomes across all age groups. They are harmonizing individual patient data from more than 20 contemporary clinical trials from North America and Europe of all ages as well as 6 institutional and regional Hodgkin lymphoma registries, and a large community oncology practice. Their goal is to enhance decision-making for pediatric and adult Hodgkin lymphoma patients and providers, given expanding treatment options and in the absence of complete acute and long-term prognostic data.

Dr Stephen Ansell and Deborah Sims – Hodgkin Lymphoma.

Dr Ansell is a leading specialist in non-Hodgkin lymphoma and Hodgkin lymphoma at the Mayo Clinic, USA. Dr Ansell spoke about the Hodgkin lymphoma – front line therapy session at ASH that he had just attended. The session highlighted a clinical trial whereby there were further use in novel therapies in the front-line setting, whereby adding Brentuximab Vedotin & a PD-1 inhibitor and reducing some of the standard chemotherapy that was bleomycin, showed outstanding results. The outcomes also reduced the toxicity for patients receiving this treatment in comparison to standard therapy. Standard therapy in Hodgkin lymphoma have high over all response rates where around 90% patient reach a complete metabolic response. Many trials in Hodgkin lymphoma are currently aimed at reducing the toxicity profile and late effects for these patients.

Marginal Zone Lymphoma

Dr Sasanka Handunetti – Phase II Study in Relapsed or Refractory Marginal Zone Lymphoma.

Dr Handunetti discussed a poster presentation from the team at Peter MacCallum Cancer Centre during the meeting of the use of ibrutinib in combination with venetoclax for patients with relapsed or refractory Marginal Zone Lymphoma (MZL). MZL is an incurable disorder that there is no standard of care treatment in the relapsed or refractory setting. Both of these medications were seen to have evidence of activity and tolerability as monotherapies (single agents) and this study aimed to evaluate the response as a combination therapy.

Central Nervous System Lymphoma

Dr Katherine Lewis – Primary Central Nervous System Lymphoma (PCNSL).

Dr Lewis discussed a poster presentation at ASH 2019 that looked at the outcomes for patients with primary or secondary central nervous system (brain and spine) lymphoma treated with Ibrutinib (BTK inhibitor). This is a rare and aggressive lymphoma where this patient group has a poor prognosis with often treated with intensive combination chemotherapy regimens. This was a retrospective study that collected information from across Australia and New Zealand of 16 patients who were treated with monotherapy Ibrutinib in the relapsed/refractory setting. Although a small number of patients, the results were promising, with response rates of up to 81%.

Waldenstrom’s Macroglobulinaemia

Prof Mathias Rummel – Waldenstrom’s Macroglobulinaemia & the StiL trial.

Covers the 2-year results post the StiL study looking at maintenance Rituximab vs observation post bendamustine-rituximab. Results show that maintenance rituximab does not improve overall survival. Prof Rummel also provides an overview of current management of WM.

T-cell Lymphoma

Peripheral T-cell Lymphoma

Dr Jasmine Zain, MD – discusses the most impressive studies in PTCL presented at ASH 2019.

(Thanks to OBRoncology).

Dr. Zain, Director of the T-cell Lymphoma Program, Department of Hematology and Hematopoietic Cell Transplantation, Toni Stephenson Lymphoma Center, City of Hope, discusses the most impressive studies in the treatment of peripheral T-cell lymphoma (PTCL) presented at ASH 2019.

Dr Jasmine Zain – How treatment for peripheral T-cell lymphoma has evolved.

(Thanks to OBRoncology).

Dr. Zain, Director of the T-cell Lymphoma Program, Department of Hematology and Hematopoietic Cell Transplantation, Toni Stephenson Lymphoma Center, City of Hope, considers how peripheral T-cell lymphoma (PCL) therapy has evolved in recent years.

Dr Jasmine Zain – Novel approaches to treat PTCL including CAR T-cell therapy.

(Thanks to OBRoncology).

Dr. Zain, Director of the T-cell Lymphoma Program, Department of Hematology and Hematopoietic Cell Transplantation, Toni Stephenson Lymphoma Center, City of Hope, tells us about some of the novel approaches in development for the treatment of peripheral T-cell lymphoma (PTCL).

Dr Timothy Illidge, explains the purpose of targeting PTCL.

(Thanks to OBRoncology).

Dr. Illidge, Professor of Targeted Therapy and Oncology, Division of Cancer Sciences, The Christie Hospital, University of Manchester, explains the purpose of targeting peripheral t-cell lymphoma (PTCL).

Lymphoma Management

ASH 2019 Interview – Dr Nada Hamad – Connecting City-Rural Health Teams and The Rural Patient

Chimeric Antigen Receptor (CAR) T-cell Therapy

ASH 2019 Interview – Dr Collin Chin – CAR T-cell therapy in aggressive lymphomas
ASH 2019 Interview – Dr Tanya Siddiqi – CAR T-cell in relapsed/refractory CLL
ASH 2019 Interview – Dr Loretta Nastoupil, CAR T-cell therapy clinical trials update
ASH 2019 Interview – Dr Loretta Nastoupil – CAR T-cell therapy update

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