CIRCULATING B CELL SUBPOPULATIONS IN INDOLENT B CELL LYMPHOMA
Methods for treating B cell lymphomas are provided. B cell lymphomas patients suitable for treatments can be identified based on the baseline B cell subset frequencies. For instance, increased frequency of transitional (CD10+) B cells within total nave B cells or within total B cells predicts poor response to kinase inhibitors. By contrast, having an increased nave B cells to total B cells frequency without an increased transitional (CD10+) B cell frequency predicts good response to the kinase inhibitors. Having a decreased frequency of nave B cells of the total B cell population with a corresponding increase in frequency of memory switched and double negative B cells of the total B cell population also predicts good response to the kinase inhibitors. Once the patients are identified, the patients can be suitably treated with the kinase inhibitors such as cerdulatinib.
1 . A method for treating a B cell lymphoma, comprising administering a kinase inhibitor to a patient suffering from the B cell lymphoma, wherein the kinase inhibitor is selected from the group consisting of a PI3K inhibitor, a SYK inhibitor, a JAK inhibitor, and a BTK inhibitor, and wherein the patient
(a) does not have increased frequency of transitional (CD10+) B cells within total naive B cells or within total B cells; or
(b) has decreased frequency of naive B cells within total B cells, and has increased frequency of memory switched B cells or double negative B cells within total B cells,
wherein the increase and decrease are as compared to a corresponding healthy subject not having the B cell lymphoma.
2 . The method of claim 1 , wherein no more than 30% of the naive B cells of the patient are transitional B cells.
3 . The method of claim 1 , wherein no more than 25% of the total B cells of the patient are transitional B cells.
4 . The method of any preceding claim , wherein the B cell lymphoma is non-Hodgkin lymphoma (NHL) .
5 . The method of claim 4 , wherein the NHL is indolent NHL (iNHL).
6 . The method of any one of claims 1-5 , wherein the frequencies are determined in a blood sample obtained or derived from the patient.
7 . The method of claim 6 , further comprising:
obtaining or preparing the blood sample; and
determining, in the blood sample, numbers of total B cells, transitional B cells, naive B cells, double negative B cells, switched memory B cells, or any combination thereof.
8 . The method of any preceding claim , wherein the transitional B cells comprises CD10+ transitional B cells, or CD38+ transitional B cells, or both.
9 . A method for treating a B cell lymphoma, comprising:
determining, in a blood sample isolated from a B cell lymphoma patient, numbers of total B cells, transitional B cells and/or naive B cells;
selecting the patient for treatment when the patient (a) does not have increased frequency of transitional (CD10+) B cells within total naive B cells or within total B cells; or (b) has decreased frequency of naive B cells within total B cells, and has increased frequency of memory switched B cells or double negative B cells within total B cells, wherein the increase and decrease are as compared to a corresponding healthy subject not having the B cell lymphoma; and
administering a kinase inhibitor selected from the group consisting of a PI3K inhibitor, a SYK inhibitor, a JAK inhibitor, and a BTK inhibitor to the patient.
10 . A method for identifying a patient as suitable for treatment with a kinase inhibitor, comprising
determining, in a blood sample derived from a B cell lymphoma patient, the numbers of total B cells, transitional B cells and/or naive B cells,
wherein the patient is identified as suitable for the treatment if the patient (a) does not have increased frequency of transitional (CD10+) B cells within total naive B cells or within total B cells; or (b) has decreased frequency of naive B cells within total B cells, and has increased frequency of memory switched B cells or double negative B cells within total B cells,
wherein the increase and decrease are as compared to a corresponding healthy subject not having the B cell lymphoma, and
wherein the kinase inhibitor is selected from the group consisting of a PI3K inhibitor, a SYK inhibitor, a JAK inhibitor, and a BTK inhibitor.
11 . The method of claim 9 or 10 , wherein the patient selected or identified has no more than 30% of the naive B cells being transitional B cells.
12 . The method of claim 9 or 10 , wherein the patient has no more than 25% of the total B cells being transitional B cells.
13 . The method of any one of claims 9-12 , wherein the B cell lymphoma is non-Hodgkin lymphoma (NHL) .
14 . The method of claim 13 , wherein the NHL is indolent NHL (iNHL).
15 . The method of any preceding claim , wherein the patient has not suffered from a diabetic or pre-diabetic condition prior to the administration.
16 . The method of any preceding claim , wherein the patient has had fewer than 5 prior treatments for the B cell lymphoma.
17 . The method of any preceding claim , wherein the patient has not had any prior treatment for the B cell lymphoma.
18 . The method of any preceding claim , wherein the kinase inhibitor is a PI3K inhibitor selected from the group consisting of idelalisib, IPI-145, AMG-319, TGR-1202, and BKM120.
19 . The method of any one of claims 1-17 , wherein the kinase inhibitor is a SYK inhibitor selected from the group consisting of fostamatinib, entospletinib, cerdulatinib, and TAK-659.
20 . The method of any one of claims 1-17 , wherein the kinase inhibitor is a JAK inhibitor selected from the group consisting of ruxolitinib, tofacitinib, oclacitinib, baricitinib, peficitinib, fedratinib, upadacitinib, and cerdulatinib.
21 . The method of any one of claims 1-17 , wherein the kinase inhibitor is a BTK inhibitor.
22 . The method of any one of claims 1-17 , wherein the kinase inhibitor is cerdulatinib.