David Routledge

Summary: SeaLAND (ALLG MM23, ACTRN12620000291987) was a randomized, open‐label phase III study evaluating low‐dose weekly selinexor (40 mg) plus lenalidomide (selinexor‐R) versus lenalidomide alone (R) as post‐transplant maintenance therapy for newly diagnosed, transplant‐eligible multiple myeloma. A total of 142 patients were enrolled (R = 64; selinexor‐R = 78); the trial closed early for futility. At best response, the complete response (≥CR) rate was numerically, but not significantly, higher with selinexor‐R than R (67% vs. 53%, p = 0.09). At 24 months median follow‐up, progression‐free survival (PFS) was not significantly different between selinexor‐R compared to R (hazard ratio [HR] = 1.22; 95% confidence interval [CI] 0.62–2.41; p = 0.56); 24‐month PFS rates were 73% (95% CI 57%–84%) for R and 70% (95% CI: 56%–81%) for selinexor‐R. The mean relative dose intensity (RDI) of R was lower in the selinexor‐R arm compared to R alone (68% vs. 81%, p = 0.002); the mean RDI of S was 55%. Grade ≥3 adverse events were more frequent with selinexor‐R (85% vs. 45%, p < 0.001). Common severe non‐haematological adverse events included infections (R: 6%, selinexor‐R: 19%, p < 0.01) and gastrointestinal disorders (R: 3%, selinexor‐R: 14%, p < 0.05). Selinexor‐R maintenance did not improve PFS and substantially increased toxicity. Selinexor‐R maintenance cannot be recommended for the general myeloma population; we did not observe a benefit among high‐risk disease.

Integration of clinical pharmacogenomics (PGx) within routine cancer care is limited despite frequent use of medicines impacted by PGx, evidence for the benefits of PGx, and the availability of international PGx clinical guidelines. Our study objective was to develop survey tools to assess PGx knowledge, attitudes, practices, perceptions, and education needs among (a) doctors, nurses, and pharmacists involved in cancer care (healthcare professionals, HCPs) and (b) adults who have received cancer treatment or their carers (consumers), with the view to informing implementation strategies for PGx in solid and hematologic cancers. Survey tools were developed in a three‐phase (ph) mixed‐methods approach. Content was informed by systematic literature review findings and framed by determinants of behavior as informed by the Theoretical Domains Framework (ph‐1). Refinement occurred through four separate priority partnership meetings (ph‐2). Meetings focused on clinical PGx practices within select cancer streams, and consumers' knowledge, attitudes, and preferences for PGx testing. Content/face validity and health literacy (Flesch Kincaid Grade Level) assessments informed final refinements (ph‐3). Separate HCP and consumer survey tools were developed with six common sections: (1) introduction; (2) demographics; (3) experience; (4) knowledge, attitudes, practices and perceptions; (5) education; and (6) vignettes. Content and face validity were rated highly with acceptable health literacy assessments for questions within the consumer survey (median grade level 6; range 1–8). The developed survey tools will be used to generate evidence to inform local implementation strategies for PGx in cancer and promote broader integration of pharmacogenomics in routine clinical care.

Introduction: High dose therapy with Autologous Stem Cell Transplantation (ASCT) has traditionally been performed as an inpatient procedure. However, with improvements in care and patient selection it is possible to safely deliver conditioning chemotherapy and supportive care in an Daytherapy setting (Kodad SG et al., 2019). While deemed an "outpatient procedure" this method is often delivered on large day units which requires the patient to attend daily, often only spending overnight at home. To reduce these daily visits the Clinical Haematology Department of Peter MacCallum and Royal Melbourne Hospital (CHD) in collaboration with the Hospital in the Home department (HIHD) at Royal Melbourne Hospital developed an innovative program to safely deliver supportive care for Myeloma Patients undergoing ASCT at home (HIH-ASCT). The HIHD is an acute inpatient unit that exists as a "virtual" inpatient ward. Patients are reviewed daily by a HIHD Doctor with twice daily visits by a HIHD Nurse for administration of supportive care measures (e.g. intravenous electrolyte and fluid replacement) in the comfort of their home. Here we report on the safety outcomes of our HIH-ASCT program, specifically patient complications and outcomes. Methods: A retrospective case note audit identified 54 consecutive HIH-ASCT patients who received HIH-ASCT for Myeloma between 2018 and 2021 under HIHD. Patients were eligible for our HIH-ASCT program if they had Myeloma requiring ASCT; an ECOG ≤1; had not been admitted to ICU previously; lived within 30 minutes drive of the hospital; had a safe home environment (for both the patient and visiting staff) and a carer who could stay with them throughout their HIH-ASCT. While undertaking HIH-ASCT patients did not receive prophylactic antibiotics and they were not routinely given GCSF to minimise the risk of engraftment fevers. Results: Of those treated as HIH-ASCT patients the median age was 60 years (range 33-72). 39% patients were female (n=21) and 61% male (n=33). Underlying disease groups included IgA (n=8; 15%), IgG (n=35; 64%), IgM (n=1; 2%), Light Chain (n=9; 17%) and Oligosecretory (n=1; 2%). 43% had High-risk Cytogenetics. ASCT-1 (n=48; 88%), ASCT-2 (n=5; 9%) and one patient underwent a ASCT-Tandem (both under HIHD). Conditioning regimes included Melphalan200 (n=37; 68%), Velcade-Melphan200 (n=13; 23%) and Carfilzomib-Melphalan200 (n=5; 9%). The average stem dose was 3.80 x10 ⁶/kg (range 2.14-8.4). Median time to Neutrophil engraftment was 12 days (range = 10-21) and Platelet engraftment 12 days (range = 8-18). The total number of bed days saved through the HIH-ASCT program was 466, with a median length of stay (LOS) under the HIHD team of 9 days (Range = 3-14). In addition, 3 patients were not readmitted to the hospital (6%) and were discharged directly from the HIHD team. The most common reason for readmission was fever (n=43; 80%), of which only 11 were culture positive, and diarrhoea (n=44; 81%). Only 1 patient required intensive care support. There were no deaths. The median LOS as an inpatient once readmitted was 6 days (range = 2-27). In regards to cost savings, an acute inpatient bed under the CHD is approximately $1300 USD versus $900 USD per day for a HIHD bed. This equated to a potential cost saving for the CHD of approximately $186000 USD. Conclusion: The delivery of supportive care for patients undergoing HIH-ASCT in is both safe and effective with comparable outcomes for what would be expected for an inpatient cohort. It resulted in a median of 9 bed days saved per patient (total number of bed days saved = 466). This is important as it allowed our department to increase bed capacity across the unit without the associated costs of building a new ward. In addition, during our COVID-19 outbreaks the HIH-ASCT program has allowed us to continue to deliver optimal patient care, while minimising the infection risk for our patients. More recently we have introduced remote monitoring (e.g. temperature, heart rate, blood pressure and oxygen saturations) with video reviews with the aim of increasing the capacity of our HIHD and further improving the HIH-ASCT experience for our patients.

There are currently limited Australian data on the outcomes of autologous stem cell transplantation (ASCT) in elderly multiple myeloma (MM) patients. We present the largest cohort of elderly MM patients aged ≥65 years undergoing ASCT in Australia and report their outcomes based on our two‐centre experience. Our study affirms that ASCT is well tolerated, safe and effective in elderly MM patients aged ≥65 years and should be considered an important component of treatment in patients who are fit enough for the procedure.

Summary: The last 5 to 10 years have been marked by considerable advances in both our understanding of the biology and treatment of chronic lymphocytic leukaemia (CLL). Fludarabine‐based immuno‐chemotherapy is the current standard of care for first line therapy in younger fit patients and although this can be highly effective its use in older co‐morbid patients is limited by toxicity, and the prognosis for patients with high risk or fludarabine‐refractory disease is poor. The introduction of new antibodies has however, facilitated the use of immuno‐chemotherapy in co‐morbid patients. Beyond this, the recognition that CLL cells are critically dependent on B‐cell receptor (BCR) signalling and interactions with the cellular micro‐environment for proliferation and survival has led to the investigation of BCR inhibitors in CLL treatment. These have been shown to be highly effective although a number of questions remain about how they should be optimally used in clinical practice.