Imnovid® approved for use in Scotland
The Scottish Medicines Consortium (SMC) has recently accepted the use of Imnovid (pomalidomide) in combination with dexamethasone for the treatment of relapsed and refractory myeloma patients who have received at least two prior treatments, including Velcade® (bortezomib) and Revlimid® (lenalidomide), and who have evidence of disease progression following their last treatment. The approval follows a resubmission by Celgene after it was originally turned down earlier in the year with the inclusion of a Patient Access Scheme (PAS) to improve the cost-effectiveness of the drug.

Ixazomib granted FDA breakthrough therapy status for the treatment of relapsed or refractory AL amyloidosis
Takeda, the Japanese pharmaceutical company, has announced its investigational drug ixazomib (MLN 9708) has been granted breakthrough therapy status by the US Food and Drug Administration (FDA) for the treatment of relapsed or refractory AL amyloidosis. Ixazomib is an oral proteasome inhibitor which in early clinical trials has shown promise in heavily pretreated AL amyloidosis patients. This is the first proteasome inhibitor and first investigational treatment for AL amyloidosis to receive this designation and should help expediate its development as a treatment for these patients.
Publication of data from the Kyprolis® Phase III ASPIRE trial
Results of the Phase III ASPIRE trial comparing the treatment of relapsed myeloma patients with Kyprolis (carfilzomib), Revlimid and dexamethasone versus Revlimid and dexamethasone have demonstrated that addition of Kyprolis to Revlimid and dexamethasone generated deep and durable responses, and increased progression free survival (PFS). Published in the New England Journal of Medicine, the results showed that PFS was significantly improved with Kyprolis (median 26.3 months versus 17.6 months in control group) although median overall survival had not yet been reached. Interestingly, patients in the Kyprolis group reported better health-related quality of life than those in the control group. 
Orphan drug designation for novel drug I-131-CLR1404 as a treatment for myeloma
The US biopharmaceutical company, Cellectar Biosciences, has announced that the FDA has granted orphan drug designation for its proprietary drug, I-131-CLR1404, as a treatment for myeloma. I-131-CLR1404 is a small molecule, broad-spectrum radiopharmaceutical comprised of a unique optimised phospholipid ether (PLE) analogue that acts as a cancer-targeted delivery and retention vehicle. Orphan drug status will support the company’s efforts to move I-131-CLR1404 through clinical development in a number of malignancies. A proof-of-concept trial in myeloma is expected to commence in the new year.
ASH 2014 meeting highlights
Highlights of the key data presented at the 56th Annual Meeting of the American Society of Hematology on 6 – 9 December in San Francisco include:

• Results of a Phase II trial of ixazomib maintenance treatment in newly diagnosed myeloma patients following induction treatment with ixazomib in combination with Revlimid and dexamethasone showing benefit with continued ixazomib treatment. Of the 21 patients who received ixazomib maintenance until disease progression (median treatment duration of 26.6 months), 52% achieved a complete response or better, with 48% of them improving their response during the maintenance period. Ixazomib maintenance was well tolerated with only 10% of patients requiring dose reduction. These results support the ongoing Phase III trial of the oral proteasome inhibitor in the maintenance setting. To view abstract, click here
   
• Data from the randomised Phase III ASPIRE trial evaluating the combination of Kyprolis with Revlimid and dexamethasone for relapsed myeloma patients showing improvement in PFS by 8.7 months compared to Revlimid and dexamethasone. 87% of patients receiving Kyprolis, Revlimid and dexamethasone responded to treatment compared to 67% of patients receiving Revlimid and dexamethasone, with 32% of patients achieving a stringent CR or CR compared to 9% in the control group. To view abstract, click here
   
• Results of the Phase I/II trial of the anti-CD38 monoclonal antibody, daratumumab, in combination with Revlimid and dexamethasone for relapsed and/or refractory myeloma patients showed that all patients (n=13) in Phase I responded to treatment while in Phase II, 87% of patients (n=30) had thus far responded. Of these, 7% had achieved CR; 43% achieved VGPR and 37% achieved PR. Patients were continuing to be followed up but the results appeared to provide further evidence of the effectiveness of daratumumab as potential treatment for myeloma.To view abstract, click here
   
• Updated results of a Phase Ib trial of the anti-CD38 monoclonal antibody SAR650984 in combination with Revlimid and dexamethasone as a treatment for relapsed and refractory myeloma showing promising activity in heavily pretreated patients who had received a median of seven prior treatments. Overall, 53% of patients (n=31) achieved a partial response or better and median PFS was 6.2 months, further adding to the evidence that SAR650984 may be a promising potential treatment for myeloma. To view abstract, click here
   
• Results of a study demonstrating that next generation sequencing may be superior to multicolour flow cytometry in the assessment of minimal residual disease (MRD), as all patients with residual disease by multicolour flow cytometry were also MRD positive by sequencing. However, sequencing detected patients with MRD who were negative by multicolour flow cytometry, suggesting greater sensitivity. To view abstract, click here

Other data highlighting promising novel drugs and approaches as potential treatments for myeloma included:

• Ibrutinib, a first-in-class oral Bruton’s tyrosine kinase (BTK) inhibitor either as a monotherapy or in combination with dexamethasone. Abstract
   
• PVX-410, a multi-peptide vaccine being developed to prevent the progression from smouldering myeloma to symptomatic myeloma. Abstract
   
• Chimeric antigen receptor-modified T-cell (CAR-T) therapy involving engineered autologous T cells directed against myeloma specific antigens. Abstract
   
• Nivolumab (BMS936558), an anti-PD-1 receptor blocking antibody, potentiating T cell activity. Abstract

First results from MUK six presented at ASH 2014
Initial data from MUK six, the second trial from the Myeloma UK Clinical Trial Network to have completed recruitment, were presented at the ASH 2014 Annual Meeting in San Francisco.
MUK six is a multi-centre Phase I/IIa trial evaluating panobinostat in combination with Velcade, thalidomide and dexamethasone (VTD-P) followed by panobinostat maintenance in relapsed and/or refractory myeloma patients.
Presented in poster format, Principal Investigator, Dr Rakesh Popat, University College Hospital, London reported that the recommended dose of panobinostat was established at 20mg and the combination of VTD-P was safe and well tolerated. In an intent-to-treat analysis, 15 out of 24 patients receiving the recommended dose of 20mg had achieved at least a partial response.
Chief Executive of Myeloma UK, Eric Low said, “We are delighted to have been given the opportunity to present the results of MUK six at ASH. As these are still early data, we look forward to learning more about the outcomes of the trial in due course.”
To view the abstract, click here
 

Myeloma UK Patient and Family Infodays

The dates and locations of the 2015 Patient and Family Myeloma Infodays are now available. We will be holding 11 Myeloma Infodays and one AL amyloidosis Infoday across the UK in 2015.

Details of all 2015 Infodays can be found on our website

The first Infoday of 2015 takes place on Saturday 28 February at the Nottingham Belfry Hotel, Nottingham, chaired by Dr Cathy Williams, Nottingham University Hospitals, Nottingham.

Please remind your patients, their families and carers to register for this and other upcoming Infodays. Further details of all Infodays can be found here

If you would like any posters or flyers for the Infodays, contact nicola.o’neill@myeloma.org.uk

If you are interested in attending or taking part in an Infoday, contact hannah.bingham@myeloma.org.uk
Places for Infodays can be booked by:

    Phone: (0)131 557 3332
    Email: nicola.o’neill@myeloma.org.uk

For other Myeloma UK news, click here

• A reminder that the Royal College of Nursing (RCN) Education Forum national conference is being held on 10 – 11 March 2015 at the East Midlands Conference Centre, Nottingham. For further information, click here
   
• The 41st Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) takes place on 22 – 25 March 2015 at the Istanbul Congress Center, Istanbul, Turkey. For more information, click here
   
• The 55th Annual Scientific Meeting of the British Society of Haematology (BSH)) is taking place at the Edinburgh International Conference Centre, Edinburgh on 20 – 22 April 2015. The deadline for abstract submission is 13 January 2015. For more information and to register, click here
   
• The RCN 2015 Congress and Exhibition is being held on 21 – 25 June 2015 at the Bournemouth International Centre, Bournemouth. For more details, click here

Current treatment

Efficacy and safety of bortezomib-based retreatment at the first relapse in multiple myeloma patients: a retrospective study.
Oriol A et al. Hematology. 2014 Dec 10. [Epub ahead of print].
Complications of myeloma and its treatments

Bortezomib-induced acute pancreatitis: Case report and review of the literature.
Talamo G et al. J Oncol Pharm Pract. 2014 Dec 15. pii: 1078155214563813. [Epub ahead of print].
Risks and burden of viral respiratory tract infections in patients with multiple myeloma in the era of immunomodulatory drugs and bortezomib: experience at an Australian Cancer Hospital.
Teh BW et al. Support Care Cancer. 2014 Dec 10. [Epub ahead of print].
The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion.
László E et al. Acta Biol Hung. 2014 Dec;65(4):369-78. doi: 10.1556/ABiol.65.2014.4.1.
The Cause of Follicular Spicules in Multiple Myeloma.
Hosler GA et al. JAMA Dermatol. 2014 Dec 3. doi: 10.1001/jamadermatol.2014.4379. [Epub ahead of print].
The Cause of Follicular Spicules in Multiple Myeloma-Reply.
van Boheemen S et al. JAMA Dermatol. 2014 Dec 3. doi: 10.1001/jamadermatol.2014.4385. [Epub ahead of print].
Case series discussion of cardiac and vascular events following carfilzomib treatment: possible mechanism, screening, and monitoring.
Chari A et al. BMC Cancer. 2014 Dec 4;14(1):915.
Light chain crystalline kidney disease: diagnostic urine microscopy as the “liquid kidney biopsy”.
Luciano RL et al. Clin Nephrol. 2014 Dec;82(12):387-91. doi: 10.5414/CN108424.
Supportive care

Pain reduction after percutaneous vertebroplasty for myeloma-associated vertebral fractures.
Simony A et al. Dan Med J. 2014 Dec;61(12):A4945.
Bone-targeted therapies for cancer patients and bone cell biology: where do we stand?
Berenson JR et al. Curr Opin Support Palliat Care. 2014 Dec;8(4):405-6. doi: 10.1097/SPC.0000000000000104.
General

The Role Of P2X Receptors In Bone Biology.
Jorgensen NR et al. Curr Med Chem. 2014 Dec 14. [Epub ahead of print].
A joined role of canopy and reversal cells in bone remodeling – Lessons from glucocorticoid-induced osteoporosis.
Jensen PR et al. Bone. 2014 Dec 10. pii: S8756-3282(14)00456-6. doi: 10.1016/j.bone.2014.12.004. [Epub ahead of print].
Multiple myeloma and chronic leukaemias in 2014: Improved understanding of disease biology and treatment.
San-Miguel JF et al. Nat Rev Clin Oncol. 2014 Dec 16. doi: 10.1038/nrclinonc.2014.216. [Epub ahead of print].
Are low ultraviolet B and vitamin D associated with higher incidence of multiple myeloma?
Mohr SB et al. J Steroid Biochem Mol Biol. 2014 Dec 10. pii: S0960-0760(14)00311-2. doi: 10.1016/j.jsbmb.2014.12.005. [Epub ahead of print].
‘Management multiple myeloma during pregnancy: a case report and review’
Cabañas-Perianes V et al. Hematol Oncol. 2014 Dec 10. doi: 10.1002/hon.2184. [Epub ahead of print].
Venous thromboembolism in cancer patients.
Deng A et al. Hosp Pract (1995). 2014 Dec;42(5):24-33. doi: 10.3810/hp.2014.12.1156.
Elderly multiple myeloma patients experience less deterioration in health-related quality of life than younger patients compared to a normative population: a study from the population-based PROFILES registry.
van der Poel MW et al. Ann Hematol. 2014 Dec 5. [Epub ahead of print].
Disparities in black and white patients with multiple myeloma referred for autologous hematopoietic transplantation: A single center study.
Bhatnagar V et al. Cancer. 2014 Dec 2. doi: 10.1002/cncr.29160. [Epub ahead of print].
Emergence of cancer stem cells or tumor-initiating/propagating cells and relapse in multiple myeloma.
Cahu J et al. Bull Cancer. 2014 Dec 3. [Epub ahead of print].
Multiple Myeloma.
Holstein SA et al. Hematol Oncol Clin North Am. 2014 Dec;28(6):1113-1129. doi: 10.1016/j.hoc.2014.08.010. Epub 2014 Sep 30.
Autologous stem cell transplantation in multiple myeloma is not dead but alive and well.
Martino M et al. Expert Opin Biol Ther. 2014 Nov 29:1-6. [Epub ahead of print].
Controversies in multiple myeloma: to transplant or not?
Preeshagul IR et al. Curr Hematol Malig Rep. 2014 Dec;9(4):360-7. doi: 10.1007/s11899-014-0230-5.
What We Mean When We Talk About MRD in Myeloma. A Review of Current Methods. Part 1 of a Two-Part Series.
Ely S et al. Curr Hematol Malig Rep. 2014 Dec;9(4):379-88. doi: 10.1007/s11899-014-0238-x.
Controversies in the assessment of minimal residual disease in multiple myeloma: clinical significance of minimal residual disease negativity using highly sensitive techniques.
Biran N et al. Curr Hematol Malig Rep. 2014 Dec;9(4):368-78. doi: 10.1007/s11899-014-0237-y.