Emerging Immune Targets for the Treatment of Multiple Myeloma

Abstract

We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab. We included seven clinical trials on chimeric antigen receptor (CAR) T cells. CAR T-cell targets include BCMA, CD19, KLC and CD138. A recent experience of CAR T-cell (B-cell maturation antigen) therapy in advanced MM has shown global response of 100%. The future of monoclonal antibodies and adoptive T cells for MM treatment seems promising.

The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

“…Understanding whether MIF plays a pathogenetic or beneficial role in AD is important for tailored therapeutic approaches. In the former case, tailored inhibitors of MIF that are already in the clinical setting could be considered for pilot studies, which include the tautomerase inhibitor ibudilast that is marketed for different indications and is being repurposed for immunoinflammatory diseases [70], as well as anti-MIF mAb that have completed Phase I/II testing in cancer patients and the anti-CD74 mAb milatuzumab that is approved for patients with multiple myeloma [71]. It is also worth noting that the biological function of MIF can be inhibited by nitrosylation [72], and hence nitric oxide (NO) donors may indirectly promote MIF inhibition.…”

Pancreatic Extramedullary Plasmacytoma Presenting as a Pancreatic Mass

“…8 Newer molecular targets for targeted therapy are being evaluated and experience with chimeric antigen receptor T-cell targets including BCMA (B-cell maturation antigen), CD19, KLC, CD138 has shown nearly 100% global response in patients with advanced MM. 9 In summary, we have presented a rare case of primary EMP in the pancreatic body encasing the portal vein as well as the celiac artery which was detected before the diagnosis of MM. Our case was one of the high-grade EMPs that was managed by the currently recommended chemo-radiation therapy guidelines without a favorable outcome thus pointing the need for further studies evaluating adjuvant treatment regimens (based on novel agents) for these high-risk patients.…”

Successful eradication of leptomeningeal plasma cell disease

“…Monoclonal antibodies, in particular elotuzumab and daratumumab, are also emerging as therapeutic alternatives in MM. Clinical trials regarding PCL or CNS disease do not exist, but a recent case report describes promising results regarding daratumumab and CNS disease [ 21 ], supporting further investigation of immunotherapy in aggressive plasma cell diseases [ 22 ]. CNS radiotherapy has proven beneficially as consolidation therapy in lymphoproliferative CNS disease and was considered for our patient.…”