Methods for treatment using adoptive cell therapy

A method of assessing the risk of developing a toxicity after administration of a cell therapy, the method comprising:

• (a) assessing one or more parameters in a subject, wherein the one or more parameters is selected from the level, amount or concentration of LDH, ferritin or C-reactive protein (CRP) in a biological sample from the subject, or is a sum of product dimensions (SPD) of a tumor in the subject;
• wherein the subject is a candidate for treatment with the cell therapy, said cell therapy comprising a dose of genetically engineered cells expressing a recombinant receptor;
• and
• wherein the assessing is carried out prior to administering the cell therapy and/or said biological sample or tumor does not comprise the recombinant receptor and/or said engineered cells;
• and
• (b) identifying if the subject is as at risk of toxicity wherein the subject is at risk of toxicity if the one or more parameters is above a threshold level and the subject is not at risk of toxicity if the one or more parameters is at or below a threshold level, wherein:
• (i) the parameter is ferritin, and the threshold level is above at or about 1000 nanograms per milliliter, 2000 nanograms per milliliter, 3000 nanograms per milliliter, 4000 nanograms per milliliter, 5000 nanograms per milliliter, 6000 nanograms per milliliter, 7000 nanograms per milliliter or 8000 nanograms per milliliter;
• and/or
• (ii) the parameter is CRP, and the threshold level is above at or about 5 milligrams per liter, 10 milligrams per liter, 15 milligrams per liter, 20 milligrams per liter, 25 milligrams per liter, 30 milligrams per liter, 40 milligrams per liter or 50 milligrams per liter.

A method of identifying a subject, the method comprising:

• (a) assessing one or more parameters in a subject, wherein the one or more parameters is selected from the level, amount or concentration of LDH, ferritin or C-reactive protein (CRP) in a biological sample from the subject, or is a sum of product dimensions (SPD) of a tumor in the subject;
• wherein the subject is a candidate for treatment with a cell therapy, said cell therapy comprising a dose of genetically engineered cells expressing a recombinant receptor;
• and
• wherein the assessing is carried out prior to administering the cell therapy and/or said biological sample or tumor does not comprise the recombinant receptor and/or said engineered cells;
• and
• (b) identifying a subject who has a risk of developing a toxicity after administration of a cell therapy, wherein the subject is at risk of toxicity if the one or more parameters is above a threshold level and the subject is not at risk of toxicity if the one or more parameters is at or below a threshold level, wherein:
• (i) the parameter is ferritin, and the threshold level is above at or about 1000 nanograms per milliliter, 2000 nanograms per milliliter, 3000 nanograms per milliliter, 4000 nanograms per milliliter, 5000 nanograms per milliliter, 6000 nanograms per milliliter, 7000 nanograms per milliliter or 8000 nanograms per milliliter;
• and/or
• (ii) the parameter is CRP, and the threshold level is above at or about 5 milligrams per liter, 10 milligrams per liter, 15 milligrams per liter, 20 milligrams per liter, 25 milligrams per liter, 30 milligrams per liter, 40 milligrams per liter or 50 milligrams per liter.

A method of treatment, comprising:

• (a) assessing one or more parameters in a subject, wherein the one or more parameters is selected from the level, amount or concentration of LDH, ferritin or C-reactive protein (CRP) in a biological sample from the subject, or is a sum of product dimensions (SPD) of a tumor in the subject;
• wherein the subject is a candidate for treatment with a cell therapy, said cell therapy comprising a dose of genetically engineered cells expressing a recombinant receptor;
• and
• wherein the assessing is carried out prior to administering the cell therapy and/or said biological sample or tumor does not comprise the recombinant receptor and/or said engineered cells;
• and
• (b) identifying if the subject is as at risk of toxicity wherein the subject is at risk of toxicity if the one or more parameters is above a threshold level and the subject is not at risk of toxicity if the one or more parameters is at or below a threshold level, wherein:
• (i) the parameter is ferritin, and the threshold level is above at or about 1000 nanograms per milliliter, 2000 nanograms per milliliter, 3000 nanograms per milliliter, 4000 nanograms per milliliter, 5000 nanograms per milliliter, 6000 nanograms per milliliter, 7000 nanograms per milliliter or 8000 nanograms per milliliter;
• and/or
• (ii) the parameter is CRP, and the threshold level is above at or about 5 milligrams per liter, 10 milligrams per liter, 15 milligrams per liter, 20 milligrams per liter, 25 milligrams per liter, 30 milligrams per liter, 40 milligrams per liter or 50 milligrams per liter;
• and
• (c) following or based on the results of the assessment, administering to the subject the cell therapy, and, optionally, an agent or other treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity.

A method of assessing the risk of developing a toxicity after administration of a cell therapy, the method comprising:

• (a) assessing the peak concentration of genetically engineered cells expressing a recombinant receptor in a biological sample from a subject that has been previously administered a cell therapy comprising the genetically engineered cells;
• and
• (b) identifying if the subject is as at risk of toxicity wherein the subject is at risk of toxicity if the peak concentration of genetically engineered cells is above a threshold level and the subject is not at risk of toxicity if the peak concentration of genetically engineered cells is at or below a threshold level, wherein:
• the threshold level is above at or about 300 cells per microliter, 400 cells per microliter, 500 cells per microliter, 600 cells per microliter, 700 cells per microliter, 800 cells per microliter, 900 cells per microliter or 1000 cells per microliter.

A method of identifying a subject, the method comprising:

• (a) assessing the peak concentration of genetically engineered cells expressing a recombinant receptor in a biological sample from a subject that has been previously administered a cell therapy comprising the genetically engineered cells;
• and
• (b) identifying a subject who has a risk of developing a toxicity after administration of a cell therapy, wherein the subject is at risk of toxicity if the peak concentration of genetically engineered cells is above a threshold level and the subject is not at risk of toxicity if the peak concentration of genetically engineered cells is at or below a threshold level, wherein:
• the threshold level is above at or about 300 cells per microliter, 400 cells per microliter, 500 cells per microliter, 600 cells per microliter, 700 cells per microliter, 800 cells per microliter, 900 cells per microliter or 1000 cells per microliter.

A method of treatment, comprising:

• (a) assessing the peak concentration of genetically engineered cells expressing a recombinant receptor in a biological sample from a subject that has been previously administered a cell therapy comprising the genetically engineered cells;
• and
• (b) identifying if the subject is as at risk of toxicity wherein the subject is at risk of toxicity if the peak concentration of genetically engineered cells is above a threshold level and the subject is not at risk of toxicity if the peak concentration of genetically engineered cells is at or below a threshold level, wherein:
• the threshold level is above at or about 300 cells per microliter, 400 cells per microliter, 500 cells per microliter, 600 cells per microliter, 700 cells per microliter, 800 cells per microliter, 900 cells per microliter or 1000 cells per microliter;
• and
• (c) following or based on the results of the assessment, administering to the subject the cell therapy, and, optionally, an agent or other treatment capable of treating, preventing, delaying, reducing or attenuating the development or risk of development of a toxicity.