Late complications and long-term care of adult CAR T-cell patients

The suc cess of chi me ric anti gen recep tor (CAR) T-cell ther apy in adult patients with hema to logic malig nan cies has resulted in a large num ber of long-term sur vi vors who may expe ri ence late com pli ca tions dis tinct from those in the early CAR T-cell treat ment period. These late com pli ca tions, defined as occur ring more than 90 days after CAR T-cell infu sion, include cytopenias, infec tions, sec ond ary malig nan cies, and delayed neurotoxicities. Late cytopenias may be from prolonged recov ery after lymphodepleting (LD) che mo ther apy or arise anew, rais ing con cerns for recur rent pri mary dis ease or a sec ond ary malig nancy. Cytopenias are treated with sup port ive care, hema to poi etic cyto kines, and, occa sion ally, hema to poi etic stem cell sup port. LD che mo ther apy pro foundly affects B, T, and nat u ral killer cells. CD19 and B-cell matu ra tion anti gen are expressed on nor mal B cells and plasma cells, respec tively, and the targeting of these struc tures by CAR T-cell prod ucts can result in prolonged lymphopenias and hypogammaglobulinemia, mak ing infec tion an ongoing risk. Late infec tions are pre dom i nantly due to respi ra tory viruses, reactivation of her pes viruses, and Pneumocystis jirovecii. Patients may require ongo ing pro phy laxis and immu no glob u lin replace ment ther apy. Although responses may be blunted, vac ci na tions are gen er ally recommended for most adult CAR T-cell patients. Both hema to logic and solid sec ond ary malig nan cies are a known risk of CAR T-cell ther apy; retroviruses used to pro duce CAR T-cell prod ucts have resulted in T-cell can cers sec ond ary to inser tional onco gen e sis. It is essen tial to mon i tor for late com pli ca tions in adult patients receiv ing CAR T-cells by using a mul ti dis ci plin ary approach between refer ring hema tol o gist oncol o gists and cell ther apy cen ters to improve the out comes and qual ity of life for these patients.