Imprime PCG

Imprime PCG is an investigational immunotherapy that directly modulates neutrophils, monocytes and macrophages, enabling them to recognize and kill antibody-targeted cancer cells. In a phase 2 study presented at the ASCO Annual Meeting 2015, the activity and tolerability of imprime PCG in combination with rituximab and alemtuzumab were evaluated in 14 treatment-naive patients with high-risk CLL.9


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“Imprime has an interesting mechanism,” Dr Davids explained. “My sense is that it might be a way to enhance the activity of monoclonal antibodies, which I think is a worthy goal in CLL.”

Although the trial was terminated early due to slow accrual, results showed that the overall response rate was 93%, with 7 patients achieving a complete response and 2 achieving a complete response with incomplete bone marrow recovery. Grade 3 or 4 adverse events were diarrhea, transaminase increase, dehydration, gastritis, hypertension, hyponatremia, neutropenia, and febrile neutropenia.9

CD19-targeted CAR T Cells

Autologous T cells genetically modified to express CD19-targeted 19-28z chimeric antigen receptors (CARs) are being studied in a variety of hematologic malignancies, and have been found to induce durable responses in a subset of patients with relapsed/refractory CLL.10

At the ASCO Annual Meeting 2016, investigators presented an updated analysis of a phase 1 study assessing outpatient CD19-targeted CAR T cell therapy in patients with residual CLL following first-line pentostatin, cyclophosphamide, and ritximab. Eight patients achieved partial response following chemoimmunotherapy and received CAR T cells.10

After a median follow-up of 32.4 months, 2 patients achieved a complete response and a partial response each. One patient had stable disease and 1 had progressive disease. The median time to disease progression was 13.6 months. Five of 7 evaluable patients received further treatment for CLL.10

Four patients were hospitalized for pyrexia with mild cytokine release syndrome.10

“CAR T-cell therapy could eventually replace allogeneic hematopoietic cell transplantation for CLL, but I don’t see it moving up to frontline CLL therapy, as there is a fair amount of toxicity involved,” Dr Davids explained. “It is certainly not something I would put my frontline CLL patients on, but when other drugs stop working, therapeutic options with a different modality will definitely be needed.”                                       

Reference

  1. Key statistics for chronic lymphocytic leukemia. American Cancer Society website. February 23, 2016. http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-key-statistics. Accessed May 20, 2016.
  2. Byrd JC, Harrington B, O’Brien S, Jones JA, Schuh A, Devereux S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374:323-332.
  3. Byrd JC, Jones JA, Furman RR, Stephens DM, Devereux S, Brown JR, et al. Acalabrutinib, a second-generation bruton tyrosine kinase (Btk) inhibitor, in previously untreated chronic lymphocytic leukemia (CLL). J Clin Oncol. 2016;34(suppl; abstr 7521).
  4. O’Connor OA, Flinn IW, Patel MR, Fenske TS, Deng C, Brander DM, et al. TGR-1202, a novel once daily PI3K-delta inhibitor, demonstrates clinical activity with a favorable safety profile in patients with CLL and B-cell lymphoma. Poster presentation at: ASH 57th Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.
  5. Lunning MA, Vose J, Fowler N, Nastoupil L, Burger JA, Wierda W, et al. Ublituximab + TGR-1202 demonstrates activity and a favorable safety profile in relapsed/refractory B-cell NHL and high-risk CLL: Phase I results. Poster presentation at: ASH 57th Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.
  6. Mahadevan D, Pauli E, Cutter K, Dietz LA, Sportelli P, Miskin HP, et al. A Phase I trial of TGR-1202, a next generation once daily PI3K-delta inhibitor in combination with obinutuzumab plus chlorambucil, in patients with chronic lymphocytic leukemia. Poster presentation at: ASH 57th Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.
  7. O’Brien S, Patel M, Kahl B, Horwitz SM, Foss FM, Porcu P, et al. Duvelisib (IPI-145), a PI3K-δ,γ inhibitor, is clinically active in patients with relapsed/refractory chronic lymphocytic leukemia. Poster presentation at: ASH 57th Annual Meeting & Exposition; December 6-9, 2014; San Francisco, CA.
  8. Reiff SD, Guinn D, Mantel R, Smith L, Cheney C, Johnson AJ, et al. Evaluation of the novel Bruton′s tyrosine kinase (BTK) inhibitor GDC-0853 in chronic lymphocytic leukemia (CLL) with wild type or C481S mutated BTK. J Clin Oncol. 2016;34(suppl; abstr 7530).
  9. Bose N, Zent C, Weiner GJ, LaPlant B, Ottoson N, Leonardo S, et al. A phase (Ph) 1/2 trial of rituximab (RX), imprime PGG (IP), and alemtuzumab (AL) in the early treatment of patients (Pts) with high risk chronic lymphocytic leukemia (CLL). J Clin Oncol. 2015;33(suppl;abstr 7078).
  10. Geyer MB, Park JH, Riviere I, Wang X, Purdon T, Sadelain M, et al. Updated results: phase I trial of autologous CD19-targeted CAR T cells in patients with residual CLL following initial purine analog-based therapy. J Clin Oncol. 2016;34(suppl; abstr 7526).