Rob Miani joined the MMRF team as Chief Financial Officer in 2016. Most recently he was the Vice President of Finance and Corporate Controller of Aptuit, LLC, a global contract research organization providing integrated early discovery to mid-phase drug development services in the pharmaceutical industry. Rob has over 20 years of leadership experience in the private and public sectors, holding managerial positions in the renewable energy, private equity, Internet and technology industries, including Davenport Newberry, Oak Investment Partners and INT Media Group. He began his career with Arthur Anderson LLP in the Assurance and Business Advisory Services Division. Rob is a CPA and received his BS degree in Accounting from Fairfield University.
Exclusive Q&A with MMRF Board member, Dr. Ken Anderson
Exclusive Q&A with MMRF Board member, Dr. Ken Anderson
What should patients know about the three recent drug approvals in multiple myeloma? The three recent approvals are a continuation of amazing progress in this disease. Ninlaro (ixazomib) is the first oral proteasome inhibitor (it belongs to the same class as ...
What should patients know about the three recent drug approvals in multiple myeloma?
The three recent approvals are a continuation of amazing progress in this disease. Ninlaro (ixazomib) is the first oral proteasome inhibitor (it belongs to the same class as Velcade and Kyprolis). It offers patients the convenience of an oral medication that is taken once a week and is very well tolerated, ie, the side effects are manageable and it does not cause peripheral neuropathy as Velcade can in some patients. Studies have shown that it can work by itself but when combined with Revlimid and dexamethasone (Rev-dex), responses are durable and deep. I have had patients on oral maintenance Ninlaro therapy for over five years. It is also very active even when other proteasome inhibitors no longer work.
Emplicti (elotuzumab) and Darzalex (daratumumab) are the first monoclonal antitodies for multiple myeloma. These are given intravenously. They work by recognizing protein fingerprints on myeloma cells and label them for destruction by the patients own immune system. Empliciti targets SLAMF7 on myeloma cells and immune cells. When given as a single agent in clinical trials, patients achieved stable disease, but had no significant responses. When combined with Rev-dex, responses and durability are markedly improved. Empliciti is also very active even in high-risk myeloma, including patients with del17p myeloma. Darzalex targets a different surface protein – CD38 – and is active in 1/3 far advanced myeloma when used as a single agent; as with Emplicti, when combined with Rev-dex, the response rate is markedly increased.
How will these recent approvals change the way MM is treated?
These new approvals represent a major increase in the treatments we now have in our armamentarium. In the future, our task will be to determine the best way to combine these agents and move them earlier in the disease course to achieve higher and deeper responses than ever before. Because of these advances, achieving minimal residual disease negativity (ie, no myeloma can be found even with the most sensitive and cutting-edge techniques), is now the goal of many of the ongoing clinical trials. I have no doubt that we are making myeloma a chronic illness in many patients, and that cures are on horizon.
What’s next?
In my opinion, the most promising new strategies target the Achilles heels or weaknesses of the myeloma cells and can be grouped into three broad categories:
1. Targeting the myeloma cell’s ability to dispose of excess protein and degrade. In this area, we first had proteasome inhibitors and now we have the second generation proteasome inhibitors carfilzomib and Ninlaro as an oral medication; they block degradation and disposal of monoclonal proteins and myeloma cells literally fill up with their own protein and commit suicide. Now we have the histone deacetylase (HDAC) inhibitors can block the degradation of protein in the aggresome, the only other garbage disposal in MM cells. Farydak (panobinostat) is a pan-HDAC inhibitor that was FDA approved earlier this year, and more selective ones such as ricolinostat (ACY-1215) are moving forward in clinical trials, showing strong efficacy particularly when combined with the proteasome inhibitors.
2. Building out the portfolio of Immune therapy agents. First we had the IMiDs (eg, Revlimid and Pomalyst) that are now used around the world; second we now have monoclonal antibodies which label myeloma cells for destruction by the patients own immune system. Now a third class is emerging – the checkpoint inhibitors. On the surface of myeloma cells are proteins such as PD-L1 that allow the myeloma cell to camouflage itself, so that the immune system does not recognize them. Checkpoint inhibitors antibodies can remove the camouflage, taking the brakes off the immune system and allowing a patient to reject their own cancer. The fourth immune category are the vaccines, which offer the potential to generate long term protection of patients against their own myeloma, from the disease. The last is cellular therapy, eg, CAR T cell therapy, in which immune T-cells are removed from patients and then outside the body re-programmed and expanded to recognize myeloma. The cells are then re-infused as a patient’s own immune army against their own myeloma. The future will be to combine immune therapies– we’re already doing this with immunomodulatory drugs and the antibodies. Particularly exciting is the concept of vaccinating patients with smoldering multiple myeloma to stimulate an immune response against their myeloma, and then amplifying the response with immunomodulatory drugs or checkpoint inhibitors to a achieve memory immune responses; these patients may never develop active disease. The excitement of immune therapies is their potency, selectivity, and adaptability, which may be able to overcome changes myeloma cells undergo to survive and thrive despite our treatments.
3. Leveraging knowledge of genomics. With the MMRF and MMRC, we have shown that myeloma cells have extensive gene damage from the outset which is ongoing, yet the cells do not die. We have now identified the fuse in the circuit which would normally result in the death of myeloma cells with gene damage, and now have prototype medicines to restore the fuse and allow them to die. Alternatively, some myeloma cells overexpress genes like cMyc which programs them to grow and divide rapidly, increasing stress on their system. In this case we have prototype medicines to overwhelm their ability to deal with this stress and die.
There has never been a more exciting time in bench to bedside research in myeloma, offering hope and life to patients and their families, and the best is yet to come!!
