`
`
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`Attorney Docket No. 25922-819.301
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`11.
`
`The method of claim 1, wherein analyzing the mobilized plurality of cells comprises
`
`measuring the duration of an increase in the peripheral blood concentration of the mobilized plurality
`
`of cells as compared to the concentration before administration of the Btk inhibitor.
`
`12.
`
`The method of claim 11, further comprising administering a second cancer treatment regimen
`
`after the peripheral blood concentration of the mobilized plurality of cells has increased for a
`
`predetermined length of time.
`
`13.
`
`The method of claim 1, wherein analyzing the mobilized plurality of cells comprises
`
`counting the number of mobilized plurality of cells in the peripheral blood.
`
`14.
`
`The method of claim 13, further comprising administering a second cancer treatment regimen
`
`after the number of mobilized plurality of cells in the peripheral blood increases as compared to the
`
`number before administration of the Btk inhibitor.
`
`15.
`
`The method of claim 14, wherein administering the second cancer treatment regimen occurs
`
`after a subsequent decrease in the number of mobilized plurality of cells in the peripheral blood.
`
`16.
`
`The method of claim 1, wherein analyzing the mobilized plurality of cells comprises
`
`measuring the duration of an increase in the number of mobilized plurality of cells in the peripheral
`
`blood as compared to the number before administration of the Btk inhibitor.
`
`17.
`
`The method of claim 16, further comprising administering a second cancer treatment regimen
`
`after the number of mobilized plurality of cells in the peripheral blood has increased for a
`
`predetermined length of time.
`
`18.
`
`The method of claim 1, wherein analyzing the mobilized plurality of cells comprises
`
`preparing a biomarker profile for a population of cells isolated from the plurality of cells, wherein
`
`the biomarker profile indicates the expression of a biomarker, the expression level of a biomarker,
`
`mutations in a biomarker, or the presence of a biomarker.
`
`19.
`
`The method of claim 18, wherein the biomarker is any cytogenetic, cell surface molecular or
`
`protein or RNA expression marker.
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`20.
`
`The method of claim 18, wherein the biomarker is: ZAP70; t(14,18); ~-2 microglobulin; p53
`
`mutational status; ATM mutational status; del(l 7)p; del(l l)q; del(6)q; CDS; CDl lc; CD19; CD20;
`
`CD22; CD25; CD38; CD103; CD138; secreted, surface or cytoplasmic immunoglobulin expression;
`
`VH mutational status; or a combination thereof
`
`21.
`
`The method of claim 18, further comprising providing a second cancer treatment regimen
`
`based on the biomarker profile.
`
`22.
`
`The method of claim 18, further comprising not administering based on the biomarker
`
`profile.
`
`23.
`
`The method of claim 18, further comprising predicting the efficacy of a second cancer
`
`treatment regimen based on the biomarker profile.
`
`24.
`
`The method of claim 1, wherein the hematological malignancy is a chronic lymphocytic
`
`leukemia (CLL), small lymphocytic lymphoma (SLL), high risk CLL, or a non-CLL/SLL
`
`lymphoma.
`
`25.
`
`The method of claim 1, wherein the hematological malignancy is follicular lymphoma,
`
`diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, Waldenstrom's
`
`macroglobulinemia, multiple myeloma, marginal zone lymphoma, Burkitt's lymphoma, non-Burkitt
`
`high grade B cell lymphoma, or extranodal marginal zone B cell lymphoma.
`
`26.
`
`The method of claim 1, wherein the hematological malignancy is acute or chronic
`
`myelogenous (or myeloid) leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia.
`
`27.
`
`The method of claim 1, wherein the hematological malignancy is relapsed or refractory
`
`diffuse large B-cell lymphoma (DLBCL), relapsed or refractory mantle cell lymphoma, relapsed or
`
`refractory follicular lymphoma, relapsed or refractory CLL; relapsed or refractory SLL; relapsed or
`
`refractory multiple myeloma.
`
`28.
`
`The method of claim 1, wherein the Btk inhibitor forms a covalent bond with a
`
`cysteine sidechain of a Bruton's tyrosine kinase, a Bruton's tyrosine kinase homo log, or a Btk
`
`tyrosine kinase cysteine homolog.
`
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`29.
`
`The method of claim 1, wherein the irreversible Btk inhibitor is (R)-1-(3-( 4-amino-3-( 4-
`
`phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.
`
`30.
`
`The method of claim 1, wherein the amount of the irreversible Btk inhibitor is from 300
`
`mg/ day up to, and including, 1000 mg/ day.
`
`31.
`
`The method of claim 1, wherein the amount of the irreversible Btk inhibitor is from 420
`
`mg/day up to, and including, 840 mg/day.
`
`32.
`
`The method of claim 1, wherein the amount of the irreversible Btk inhibitor is about 420
`
`mg/day, about 560 mg/day, or about 840 mg/day.
`
`33.
`
`The method of claim 1, wherein the amount of the irreversible Btk inhibitor is about 420
`
`mg/day.
`
`34.
`
`The method of claim 1, wherein the AUC0_24 of the Btk inhibitor is between about 150 and
`
`about 3500 ng*h/mL.
`
`35.
`
`The method of claim 34, wherein AUC0_24 of the Btk inhibitor is between about 500 and
`
`about 1100 ng*h/mL.
`
`36.
`
`The method of claim 1, wherein the Btk inhibitor is administered orally.
`
`37.
`
`The method of claim 1, wherein the Btk inhibitor is administered once per day, twice per
`
`day, or three times per day.
`
`38.
`
`The method of claim 1, wherein the Btk inhibitor is administered until disease progression,
`
`unacceptable toxicity, or individual choice.
`
`39.
`
`The method of claim 1, wherein the Btk inhibitor is administered daily until disease
`
`progression, unacceptable toxicity, or individual choice.
`
`40.
`
`The method of claim 1, wherein the Btk inhibitor is administered every other day until
`
`disease progression, unacceptable toxicity, or individual choice.
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`41.
`
`The method of claim 1, wherein the Btk inhibitor is a front line therapy, second line therapy,
`
`third line therapy, fourth line therapy, fifth line therapy, or sixth line therapy.
`
`42.
`
`The method of claim 1, wherein the Btk inhibitor treats a refractory hematological
`
`malignancy.
`
`43.
`
`The method of claim 1, wherein the Btk inhibitor is a maintenance therapy.
`
`44.
`
`The method of claim 9, 10, 12, 14, 15, 17, or 21, wherein the second cancer treatment
`
`regimen comprises a chemotherapeutic agent, a steroid, an immunotherapeutic agent, a targeted
`
`therapy, or a combination thereof
`
`45.
`
`The method of claim 9, 10, 12, 14, 15, 17, or 21, wherein the second cancer treatment
`
`regimen comprises a B cell receptor pathway inhibitor.
`
`46.
`
`The method of claim 45, wherein the B cell receptor pathway inhibitor is a CD79A inhibitor,
`
`a CD79B inhibitor, a CD19 inhibitor, a Lyn inhibitor, a Syk inhibitor, a PI3K inhibitor, a Blnk
`
`inhibitor, a PLCy inhibitor, a PKC~ inhibitor, or a combination thereof
`
`47.
`
`The method of claim 9, 10, 12, 14, 15, 17, or 21, wherein the second cancer treatment
`
`regimen comprises an antibody, B cell receptor signaling inhibitor, a PI3K inhibitor, an IAP
`
`inhibitor, an mTOR inhibitor, a radioimmunotherapeutic, a DNA damaging agent, a proteosome
`
`inhibitor, a histone deacetylase inhibitor, a protein kinase inhibitor, a hedgehog inhibitor, an Hsp90
`
`inhibitor, a telomerase inhibitor, a Jakl/2 inhibitor, a protease inhibitor, a PKC inhibitor, a P ARP
`
`inhibitor, or a combination thereof
`
`48.
`
`The method of claim 9, 10, 12, 14, 15, 17, or 21, wherein the second cancer treatment
`
`regimen comprises chlorambucil, ifosphamide, doxorubicin, mesalazine, thalidomide, lenalidomide,
`
`temsirolimus, everolimus, fludarabine, fostamatinib, paclitaxel, docetaxel, ofatumumab, rituximab,
`
`dexamethasone, prednisone, CAL- I 01, ibritumomab, tositumomab, bortezomib, pentostatin,
`
`endostatin, or a combination thereof
`
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`49.
`
`The method of claim 9, 10, 12, 14, 15, 17, or 21, wherein the second cancer treatment
`
`regimen comprises cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, and
`
`optionally, rituximab.
`
`50.
`
`The method of claim 9, 10, 12, 14, 15, 17, or 21, wherein the second cancer treatment
`
`regimen comprises bendamustine, and rituximab.
`
`51.
`
`Themethodofclaim9, 10, 12, 14, 15, 17,or21,whereinthesecondcancertreatment
`
`regimen comprises fludarabine, cyclophosphamide, and rituximab.
`
`52.
`
`The method of claim 9, 10, 12, 14, 15, 17, or 21, wherein the second cancer treatment
`
`regimen comprises cyclophosphamide, vincristine, and prednisone, and optionally, rituximab.
`
`53.
`
`The method of claim 9, 10, 12, 14, 15, 17, or 21, wherein the second cancer treatment
`
`regimen comprises etoposide, doxorubicin, vinristine, cyclophosphamide, prednisolone, and
`
`optionally, rituximab.
`
`54.
`
`The method of claim 9, 10, 12, 14, 15, 17, or 21, wherein the second cancer treatment
`
`regimen comprises dexamethasone and lenalidomide.
`
`55.
`
`The method of claim 1, wherein the irreversible Btk inhibitor has the following structure:
`
`t_---Ar
`a
`
`wherein:
`
`La is CH2, 0, NH or S;
`
`Ar is a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl;
`
`Y is an optionally substituted group selected from among alkyl, heteroalkyl, cycloalkyl,
`
`heterocycloalkyl, aryl, and heteroaryl;
`
`- 190 -
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`Attorney Docket No. 25922-819.301
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`Z is C(=O), OC(=O), NHC(=O), C(=S), S(=O)x, OS(=O)x, NHS(=O)x, where xis 1or2;
`
`~' R7, and Rs are each independently selected from among H, substituted or unsubstituted C1-
`C4alkyl, substituted or unsubstituted C1-C4heteroalkyl, substituted or unsubstituted C3-C6cycloalkyl,
`substituted or unsubstituted Cz-C6heterocycloalkyl, C1-C6alkoxyalkyl, C1-Csalkylaminoalkyl,
`substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted aryl, substituted or
`unsubstituted heteroaryl, substituted or unsubstituted C1-C4alkyl( aryl), substituted or unsubstituted
`C1-C4alkyl(heteroaryl), substituted or unsubstituted C1-C4alkyl(C3-Cscycloalkyl), or substituted or
`
`unsubstituted C1-C4alkyl( Cz-Csheterocycloalkyl); or
`
`R7 and Rs taken together form a bond; and pharmaceutically active metabolites, or pharmaceutically
`
`acceptable solvates, pharmaceutically acceptable salts, or pharmaceutically acceptable prodrugs
`
`thereof
`
`56.
`
`The method of Claim 55, wherein La is 0.
`
`57.
`
`The method of Claim 55, wherein Ar is phenyl.
`
`58.
`
`The method of Claim 55, wherein: Z is C(=O), NHC(=O), or S(=0)2 .
`
`59.
`
`The method of Claim 55, wherein:
`
`each of R1 and Rs is H.
`
`60.
`
`The method of Claim 55, wherein:
`
`Y is a 4-, 5-, 6-, or 7-membered cycloalkyl ring; or
`
`Y is a 4-, 5-, 6-, or 7-membered heterocycloalkyl ring.
`
`61.
`
`A method for treating relapsed or refractory non-Hodgkin's lymphoma in an individual in
`
`need thereof, comprising: administering to the individual a therapeutically-effective amount of (R)-
`
`1-(3-( 4-amino-3-( 4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-
`
`one.
`
`62.
`
`The method of claim 61, wherein the non-Hodgkin's lymphoma is relapsed or refractory
`
`diffuse large B-cell lymphoma (DLBCL), relapsed or refractory mantle cell lymphoma, or relapsed
`
`or refractory follicular lymphoma.
`
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`63.
`
`The method of claim 61, wherein the amount of(R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-
`
`pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is from 300 mg/day up to, and
`
`including, 1000 mg/day.
`
`64.
`
`The method of claim 61, wherein the amount of(R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-
`
`pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is from 420 mg/day up to, and
`
`including, 840 mg/day.
`
`65.
`
`The method of claim 61, wherein the amount of(R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-
`
`pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is about 420 mg/day, about 560
`
`mg/day, or about 840 mg/day.
`
`66.
`
`The method of claim 61, wherein the amount of(R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-
`
`pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is about 420 mg/day.
`
`67.
`
`The method of claim 61, wherein the AUC0_24 of (R)-1-(3-( 4-amino-3-( 4-phenoxyphenyl)-
`
`1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is between about 150 and about
`
`3500 ng*h/mL.
`
`68.
`
`The method of claim 67, wherein AUC0_24 of the Btk inhibitor is between about 500 and
`
`about 1100 ng*h/mL.
`
`69.
`
`The method of claim 61, wherein (R)-1-(3-( 4-amino-3-( 4-phenoxyphenyl)-1H-pyrazolo[3,4-
`
`d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is administered orally.
`
`70.
`
`The method of claim 61, wherein (R)-1-(3-( 4-amino-3-( 4-phenoxyphenyl)-1H-pyrazolo[3,4-
`
`d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is administered once per day, twice per day, or
`
`three times per day.
`
`71.
`
`The method of claim 61, wherein (R)-1-(3-( 4-amino-3-( 4-phenoxyphenyl)-1H-pyrazolo[3,4-
`
`d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is administered until disease progression,
`
`unacceptable toxicity, or individual choice.
`
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`72.
`
`The method of claim 61, wherein (R)-1-(3-( 4-amino-3-( 4-phenoxyphenyl)-1H-pyrazolo[3,4-
`
`d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is administered until disease progression,
`
`unacceptable toxicity, or individual choice.
`
`73.
`
`The method of claim 61, wherein (R)-1-(3-( 4-amino-3-( 4-phenoxyphenyl)-1H-pyrazolo[3,4-
`
`d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is administered daily until disease progression,
`
`unacceptable toxicity, or individual choice.
`
`74.
`
`The method of claim 61, wherein (R)-1-(3-( 4-amino-3-( 4-phenoxyphenyl)-1H-pyrazolo[3,4-
`
`d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is administered every other day until disease
`
`progression, unacceptable toxicity, or individual choice.
`
`75.
`
`The method of claim 61, wherein (R)-1-(3-( 4-amino-3-( 4-phenoxyphenyl)-1H-pyrazolo[3,4-
`
`d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one is a second line therapy, third line therapy, fourth
`
`line therapy, fifth line therapy, or sixth line therapy.
`
`76.
`
`The method of claim 61, wherein the Btk inhibitor is a maintenance therapy.
`
`77.
`
`The method of claim 61, further comprising administering a second cancer treatment
`
`regimen.
`
`78.
`
`The method of claim 77, wherein the second cancer treatment regimen is administered after
`
`mobilization of a plurality oflymphoid cells from the non-Hodgkin's lymphoma.
`
`79.
`
`The method of claim 77, wherein the second cancer treatment regimen is administered after
`
`lymphocytosis of a plurality oflymphoid cells from the non-Hodgkin's lymphoma.
`
`80.
`
`The method of claim 77, wherein the second cancer treatment regimen comprises a
`
`chemotherapeutic agent, a steroid, an immunotherapeutic agent, a targeted therapy, or a combination
`
`thereof
`
`81.
`
`The method of claim 77, wherein the second cancer treatment regimen comprises a B cell
`
`receptor pathway inhibitor.
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`
`82.
`
`The method of claim 81, wherein the B cell receptor pathway inhibitor is a CD79A inhibitor,
`
`a CD79B inhibitor, a CD19 inhibitor, a Lyn inhibitor, a Syk inhibitor, a PI3K inhibitor, a Blnk
`
`inhibitor, a PLCy inhibitor, a PKC~ inhibitor, or a combination thereof
`
`83.
`
`The method of claim 77, wherein the second cancer treatment regimen comprises an
`
`antibody, B cell receptor signaling inhibitor, a PI3K inhibitor, an IAP inhibitor, an mTOR inhibitor,
`
`a radioimmunotherapeutic, a DNA damaging agent, a proteosome inhibitor, a histone deacetylase
`
`inhibitor, a protein kinase inhibitor, a hedgehog inhibitor, an Hsp90 inhibitor, a telomerase inhibitor,
`
`a Jakl/2 inhibitor, a protease inhibitor, a PKC inhibitor, a P ARP inhibitor, or a combination thereof
`
`84.
`
`The method of claim 77, wherein the second cancer treatment regimen comprises
`
`chlorambucil, ifosphamide, doxorubicin, mesalazine, thalidomide, lenalidomide, temsirolimus,
`
`everolimus, fludarabine, fostamatinib, paclitaxel, docetaxel, ofatumumab, rituximab,
`
`dexamethasone, prednisone, CAL- I 01, ibritumomab, tositumomab, bortezomib, pentostatin,
`
`endostatin, or a combination thereof
`
`85.
`
`The method of claim 77, wherein the second cancer treatment regimen comprises
`
`cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, and optionally, rituximab.
`
`86.
`
`The method of claim 77, wherein the second cancer treatment regimen comprises
`
`bendamustine, and rituximab.
`
`87.
`
`The method of claim 77, wherein the second cancer treatment regimen comprises
`
`fludarabine, cyclophosphamide, and rituximab.
`
`88.
`
`The method of claim 77, wherein the second cancer treatment regimen comprises
`
`cyclophosphamide, vincristine, and prednisone, and optionally, rituximab.
`
`89.
`
`The method of claim 77, wherein the second cancer treatment regimen comprises etoposide,
`
`doxorubicin, vinristine, cyclophosphamide, prednisolone, and optionally, rituximab.
`
`90.
`
`The method of claim 77, wherein the second cancer treatment regimen comprises
`
`dexamethasone and lenalidomide.
`
`- 194 -
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`91.
`
`A method for treating diffuse large B-cell lymphoma, activated B cell-like subtype (ABC-
`
`DLBCL ), in an individual in need thereof, comprising: administering to the individual an irreversible
`
`Btk inhibitor in an amount from 300 mg/day up to, and including, 1000 mg/day.
`
`92.
`
`The method of claim 91, further comprising diagnosing the individual with diffuse large B-
`
`cell lymphoma, activated B cell-like subtype (ABC-DLBCL), by determining the gene sequence of
`
`one or more biomarkers in a plurality oflymphoid cells isolated from the diffuse large B-cell
`
`lymphoma.
`
`93.
`
`The method of claim 91, wherein the irreversible Btk inhibitor is (R)-1-(3-( 4-amino-3-( 4-
`
`phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.
`
`94.
`
`The method of claim 91, wherein the Activated B cell-like (ABC) subtype of diffuse large B-
`
`cell lymphoma (DLBCL) is characterized by a CD79B mutation.
`
`95.
`
`The method of claim 94, wherein the CD79B mutation is a mutation of the immunoreceptor
`
`tyrosine-based activation motif (IT AM) signaling module.
`
`96.
`
`The method of claim 94, wherein the CD79B mutation is a missense mutation of the first
`
`immunoreceptor tyrosine-based activation motif (IT AM) tyrosine.
`
`97.
`
`The method of claim 94, wherein the CD79B mutation increases surface BCR expression and
`
`attenuates Lyn kinase activity.
`
`98.
`
`The method of claim 91, wherein the Activated B cell-like (ABC) subtype of diffuse large B-
`
`cell lymphoma (DLBCL) is characterized by a CD79A mutation.
`
`99.
`
`The method of claim 98, wherein the CD79A mutation is in the immunoreceptor tyrosine-
`
`based activation motif (IT AM) signaling module.
`
`100. The method of claim 98, wherein the CD79A mutation is a splice-donor-site mutation of the
`
`immunoreceptor tyrosine-based activation motif (IT AM) signaling module.
`
`101. The method of claim 98, wherein the CD79A mutation deletes the immunoreceptor tyrosine(cid:173)
`
`based activation motif (IT AM) signaling module.
`
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`102. The method of claim 91, wherein the Activated B cell-like (ABC) subtype of diffuse large B(cid:173)
`
`cell lymphoma (DLBCL) is characterized by a mutation in MyD88, A20, or a combination thereof
`
`103. The method of claim 102, wherein the MyD88 mutation is the amino acid substitution L265P
`
`in the MYD88 Toll/IL-I receptor (TIR) domain.
`
`104. The method of claim 91, wherein the amount of the irreversible Btk inhibitor is from 420
`
`mg/day up to, and including, 840 mg/day.
`
`105. The method of claim 91, wherein the amount of the irreversible Btk inhibitor is about 420
`
`mg/day, about 560 mg/day, or about 840 mg/day.
`
`106. The method of claim 91, wherein the amount of the irreversible Btk inhibitor is about 420
`
`mg/day.
`
`107. The method of claim 91, wherein the AUC0_24 of the Btk inhibitor is between about 150 and
`
`about 3500 ng*h/mL.
`
`108. The method of claim 107, wherein AUC0_24 of the Btk inhibitor is between about 500 and
`
`about 1100 ng*h/mL.
`
`109. The method of claim 91, wherein the irreversible Btk inhibitor is administered orally.
`
`110. The method of claim 91, wherein the irreversible Btk inhibitor is administered daily until
`
`disease progression, unacceptable toxicity, or individual choice.
`
`111. The method of claim 91, wherein the irreversible Btk inhibitor is administered every other
`
`day until disease progression, unacceptable toxicity, or individual choice.
`
`112. The method of claim 91, wherein the irreversible Btk inhibitor is a front line therapy, second
`
`line therapy, third line therapy, fourth line therapy, fifth line therapy, or sixth line therapy.
`
`113. The method of claim 91, wherein the irreversible Btk inhibitor treats a refractory
`
`hematological malignancy.
`
`114. The method of claim 91, wherein the irreversible Btk inhibitor is a maintenance therapy.
`
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`
`115. The method of claim 91, further comprising administering at least one additional cancer
`
`treatment regimen.
`
`116. The method of claim 115, wherein the additional cancer treatment regimen comprises a
`
`chemotherapeutic agent, an immunotherapeutic agent, a steroid, radiation therapy, a targeted
`
`therapy, or a combination thereof
`
`117. The method of claim 116, wherein the second cancer treatment regimen comprises an
`
`antibody, B cell receptor signaling inhibitor, a PI3K inhibitor, an IAP inhibitor, an mTOR inhibitor,
`
`a radioimmunotherapeutic, a DNA damaging agent, a proteosome inhibitor, a histone deacetylase
`
`inhibitor, a protein kinase inhibitor, a hedgehog inhibitor, an Hsp90 inhibitor, a telomerase inhibitor,
`
`a Jakl/2 inhibitor, a protease inhibitor, a PKC inhibitor, a P ARP inhibitor, or a combination thereof
`
`118. A method of determining a cancer treatment regimen for an individual with a hematological
`
`malignancy, comprising:
`
`a. administering to the individual an amount of an irreversible Btk inhibitor sufficient to
`
`mobilize a plurality of cells from the malignancy;
`
`b. analyzing the mobilized plurality of cells; and
`
`c. selecting a cancer treatment regimen.
`
`119. The method of claim 118, wherein the cancer treatment regimen comprises a
`
`chemotherapeutic agent, a steroid, an immunotherapeutic agent, a targeted therapy, or a combination
`
`thereof
`
`120. The method of claim 118, wherein the cancer treatment regimen comprises a B cell receptor
`
`pathway inhibitor.
`
`121. The method of claim 118, wherein the cancer treatment regimen comprises a CD79A
`
`inhibitor, a CD79B inhibitor, a CD 19 inhibitor, a Lyn inhibitor, a Syk inhibitor, a PI3K inhibitor, a
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`Blnk inhibitor, a PLCy inhibitor, a PKC~ inhibitor, or a combination thereof
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`Attorney Docket No. 25922-819.301
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`122. The method of claim 118, wherein the cancer treatment regimen comprises an antibody, B
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`cell receptor signaling inhibitor, a PI3K inhibitor, an IAP inhibitor, an mTOR inhibitor, a
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`radioimmunotherapeutic, a DNA damaging agent, a proteosome inhibitor, a histone deacetylase
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`inhibitor, a protein kinase inhibitor, a hedgehog inhibitor, an Hsp90 inhibitor, a telomerase inhibitor,
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`a Jakl/2 inhibitor, a protease inhibitor, a PKC inhibitor, a P ARP inhibitor, or a combination thereof
`
`123. The method of claim 118, wherein the cancer treatment regimen comprises chlorambucil,
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`ifosphamide, doxorubicin, mesalazine, thalidomide, lenalidomide, temsirolimus, everolimus,
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`fludarabine, fostamatinib, paclitaxel, docetaxel, ofatumumab, rituximab, dexamethasone,
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`prednisone, CAL- I 01, ibritumomab, tositumomab, bortezomib, pentostatin, endostatin, or a
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`combination thereof
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`124. The method of claim 118, wherein the cancer treatment regimen comprises
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`cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, and optionally, rituximab.
`
`125. The method of claim 118, wherein the cancer treatment regimen comprises bendamustine,
`
`and rituximab.
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`126. The method of claim 118, wherein the cancer treatment regimen comprises fludarabine,
`
`cyclophosphamide, and rituximab.
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`127. The method of claim 118, wherein the cancer treatment regimen comprises
`
`cyclophosphamide, vincristine, and prednisone, and optionally, rituximab.
`
`128. The method of claim 118, wherein the cancer treatment regimen comprises etoposide,
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`doxorubicin, vinristine, cyclophosphamide, prednisolone, and optionally, rituximab.
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`129. The method of claim 118, wherein the cancer treatment regimen comprises dexamethasone
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`and lenalidomide.
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