The present invention relates to a pharmaceutical combination of indole-3-carbinol or its derivatives with different BCR pathway inhibitors, such as the BTK inhibitors Ibrutinib and zanubrutinib, the TK inhibitor dasatinib or the PI3Kδ inhibitor Idelalisib, for the treatment of B lymphoid neoplasms. The invention also refers to a pharmaceutical composition comprising both types of these compounds and optionally further active compounds.
1. A pharmaceutical combination comprising: c) a compound of formula (I) <img class="EMIRef" id="45efc0f1-9a5a-4228-948f-5d05c8af9456-ib0006" /> or its derivatives, pharmaceutical acceptable salts or solvates, wherein R<1> represents an atom other than hydrogen, of electronegative nature selected from -NH<2> , -OH, -SH, -PH<2> , -CI, -Br, -F, -I, -OR, -NR<2> , -SR, - PR<2> , -CH<2>OH, -CH<2>NH<2> , -CH<2>SH, - CH<2>PH <2> , -CH<2>Cl, -CH<2>Br, -CH<2>F and -CH<2>I, and R<2> represents a substituent in position 5 or 6 of the indole ring selected from hydrogen, an alkyl group, a halogen atom selected from chlorine, bromine, fluorine or iodine, or an electronegative atom linked to alkyl chains selected from -OR, -NR<2>, -SR and PR<2>; where each R is independently an alkyl group, linear or branched and d) an inhibitor of the BCR pathway selected from ibrutinib, acalabrutinib, zanubrutinib, evobrutinib, tirabrutinib, vecabrutinib, dasatinib, idelalisib, copanlisib, duvelisib, gedatolisib, buparlisib, alpelisib, taselisib or rigosertib. 2. The pharmaceutical combination of claim 1 wherein the derivative of the compound of formula (I) is a compound of formula (II): <img class="EMIRef" id="45efc0f1-9a5a-4228-948f-5d05c8af9456-ib0007" /> wherein R<2> and R<3> are the same or different substituents and represent hydrogen, an alkyl group, a halogen atom selected from chlorine, bromine, fluorine or iodine, or an electronegative atom attached to alkyl chains selected from -OR, -NR<2>, -SR and PR<2>, where each R is independently an alkyl group, linear or branched. 3. The pharmaceutical combination of claim 1 wherein the derivative of the compound of formula (I) is a compound of formula (III): <img class="EMIRef" id="45efc0f1-9a5a-4228-948f-5d05c8af9456-ib0008" /> wherein R<1> is as defined in claim 1 and, R<2>, R<3> and R<4> are the same or different substituents and represent hydrogen, an alkyl group, a halogen atom selected from chlorine, bromine, fluorine or iodine, or an electronegative atom attached to alkyl chains selected from -OR, -NR<2>, -SR and PR<2>, where each R is independently an alkyl group, linear or branched. 4. The pharmaceutical combination of any one of claims 1 to 3 wherein the compound of formula (I) is selected from the following compounds: <img class="EMIRef" id="45efc0f1-9a5a-4228-948f-5d05c8af9456-ib0009" /> 5. The pharmaceutical combination of any one of claims 1 to 4 wherein the inhibitor or the BCR pathway is ibrutinib. 6. The pharmaceutical combination of any one of claims 1 to 5 wherein the compound of formula (I) is indole-3-carbinol and the inhibitor of the BCR pathway is ibrutinib. 7. The pharmaceutical combination of any one of claims 1 to 6 which comprises: c) a further active principle which is selected from fludarabine or cladribine. 8. A pharmaceutical combination according to any one of claims 1 to 7 for use in the treatment of B lymphoid neoplasms, preferably selected from chronic lymphocytic leukaemia, small cell lymphocytic lymphoma, Burkitt's lymphoma, diffuse large B-cell lymphoma, lymphoplasmacytic lymphoma, mantle cells lymphoma, Waldenstrom's macroglobulinemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma or multiple myeloma. 9. The pharmaceutical combination for use according to claim 8 wherein the use of components (a), (b) and (c) is simultaneous, separate or sequential. 10. The pharmaceutical combination for use according to any one of claims 8 to 9 wherein the use of components (a), (b) and (c) is by oral or intravenous administration. 11. A pharmaceutical composition comprising the pharmaceutical combination according to any one of claims 1 to 7 and at least one acceptable carrier. 12. A pharmaceutical composition according to claim 11 for use in the treatment of B lymphoid neoplasms, preferably selected from chronic lymphocytic leukaemia, small cell lymphocytic lymphoma, Burkitt's lymphoma, diffuse large B-cell lymphoma, lymphoplasmacytic lymphoma, mantle cells lymphoma, Waldenstrom's macroglobulinemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma or multiple myeloma. 13. The pharmaceutical composition for use according to claim 12 wherein the composition is used by oral or intravenous administration. 14. The pharmaceutical composition for use according to any one of claims 12 or 13 which comprises a further active principle selected from fludarabine or cladribine.