Method for identification of cancer patients with durable benefit from immunotherapy in overall poor prognosis subgroups
A blood-based sample from a cancer patient is subject to mass spectrometry and the resulting mass spectral data is classified with the aid of a computer to see if the patient is a member of a class of patients having a poor prognosis. If so, the mass spectral data is further classified with the aid of the computer by a second classifier which identifies whether the patient is nevertheless likely to obtain durable benefit from immunotherapy drugs, e.g., immune checkpoint inhibitors, anti-CTLA4 drugs, and high dose interleukin-2.
1. A method for treatment of a lung cancer patient, a renal cell carcinoma patient, or a melanoma patient comprising the steps of:
(a) conducting a mass spectrometer test on a blood-based sample of the cancer patient to obtain a mass spectrum; performing one or more pre-processing steps on the mass spectrum; obtaining integrated intensity values of selected features in the mass spectrum at one or more m/z ranges; using the integrated intensity values in a first stage classification algorithm using a training set comprising class-labeled spectra produced from blood-based samples from the same type of cancer patients to identify the patient as being in a class of patients determined to be a poor prognosis subgroup,
(b) identifying the patient as being in the class of patients determined to be a poor prognosis subgroup, using the integrated intensity values in a second stage classification algorithm using a training set comprising class-labeled spectra produced from blood-based samples from the same type of cancer patients treated with an immunotherapy drug to obtain a class label of Late or the equivalent which identifies the patient as likely to have durable benefit from an immunotherapy drug; and
(c) administering to the patient having a class label of Late or the equivalent an immunotherapy drug.
2. The method of claim 1 , wherein the immunotherapy drug comprises an antibody drug blocking ligand activation of the PD-1 checkpoint protein, anti-CTLA4 drugs, high dose interleukin-2, and combination therapies.
3. The method of claim 1 , wherein the immunotherapy drug comprises a combination of two immunotherapy drugs.
4. A method for treatment of a lung cancer patient, a renal cell carcinoma patient, or a melanoma patient comprising classifying mass spectral data from a blood-based sample from a lung cancer patient, a renal cell carcinoma patient, or a melanoma patient with a computer configured as a classifier, comprising the steps of: conducting a mass spectrometer test on a blood-based sample of the cancer patient to obtain a mass spectrum; performing one or more pre-processing steps on the mass spectrum; obtaining integrated intensity values of selected features in the mass spectrum at one or more m/z ranges; using the integrated intensity values in a first stage classification algorithm using a training set comprising class-labeled spectra produced from blood-based samples from the same type of cancer patients to identify whether the patient is a member of a subgroup of patients having a poor prognosis, and further, identifying the patient as being in the class of patients determined to be a poor prognosis subgroup, using the integrated intensity values in a second stage classification algorithm using a training set comprising class-labeled spectra produced from blood-based samples from the same type of cancer patients treated with an immunotherapy drug to generate a class label of Early or the equivalent or Late or the equivalent, wherein a class label of Late or the equivalent indicates the patient is likely to obtain durable benefit from immunotherapy drugs, and administering to the patient having a class label of Late or the equivalent an immunotherapy drug.
5. The method of claim 4 , wherein the immunotherapy drug comprises an antibody drug blocking ligand activation of the PD-1 checkpoint protein, anti-CTLA4 drugs, high dose interleukin-2, and combination therapies.
6. The method of claim 4 , wherein the immunotherapy drug comprises a combination of two immunotherapy drugs.
7. A method for treatment of a lung cancer patient, a renal cell carcinoma patient, or a melanoma patient comprising the steps of:
(a) conducting a mass spectrometer test on a blood-based sample of the cancer patient to obtain a mass spectrum; performing one or more pre-processing steps on the mass spectrum; obtaining integrated intensity values of selected features in the mass spectrum at one or more m/z ranges as shown in a table below
Feature Definitions
Left
m/z
Center m/z
Right m/z
3071.217
3085.189
3099.162
3099.644
3111.208
3122.771
3124.217
3144.212
3164.207
3192.341
3210.692
3229.043
3230.998
3243.532
3256.066
3296.707
3322.484
3348.261
3348.743
3363.679
3378.615
3379.097
3390.661
3402.224
3402.706
3418.124
3433.542
3434.506
3443.901
3453.297
3454.261
3462.933
3471.606
3486.542
3503.888
3521.233
3530.869
3553.033
3575.196
3583.137
3593.094
3603.051
3671.811
3682.716
3693.621
3694.825
3704.05
3713.275
3713.375
3723.478
3733.581
3759.25
3772.741
3786.232
3786.267
3795.511
3804.756
3805.438
3818.133
3830.828
3832.004
3841.641
3851.277
3877.777
3888.136
3898.495
3899.283
3907.43
3915.577
3915.701
3927.75
3939.799
3940.413
3952.458
3964.504
3995.34
4009.553
4023.767
4024.145
4031.508
4038.872
4039.254
4051.399
4063.544
4080.139
4094.835
4109.53
4112.173
4119.373
4126.573
4127.254
4133.389
4139.524
4165.916
4170.823
4175.73
4198.946
4210.815
4222.684
4252.63
4262.507
4272.384
4272.866
4287.802
4302.738
4322.975
4336.947
4350.92
4351.402
4359.834
4368.265
4369.229
4380.07
4390.911
4392.356
4408.979
4425.602
4426.151
4433.527
4440.903
4445.65
4462.521
4479.392
4493.056
4506.065
4519.074
4539.6
4546.345
4553.091
4553.295
4565.565
4577.835
4578.09
4590.487
4602.884
4610.619
4621.942
4633.264
4633.746
4642.419
4651.091
4668.351
4674.256
4680.16
4680.315
4686.375
4692.434
4694.454
4714.187
4733.919
4745.595
4755.26
4764.925
4767.31
4773.529
4779.749
4780.015
4789.426
4798.836
4801.9
4818.041
4834.181
4836.109
4856.827
4877.545
4878.027
4891.999
4905.972
4927.529
4935.668
4943.807
4948.646
4959.134
4969.622
4970.088
4977.701
4985.314
4986.713
4999.065
5011.417
5012.505
5022.06
5031.616
5033.636
5041.171
5048.707
5049.071
5067.139
5085.208
5087.135
5104.48
5121.826
5121.888
5127.87
5133.852
5134.353
5148.085
5161.816
5164.707
5176.994
5189.28
5211.228
5223.658
5236.088
5263.479
5288.052
5312.625
5330.753
5340.697
5350.642
5351.59
5362.357
5373.124
5395.675
5407.035
5418.395
5419.379
5428.197
5437.016
5442.725
5449.541
5456.357
5503.424
5519.324
5535.224
5537.824
5549.322
5560.82
5561.13
5570.453
5579.775
5666.474
5674.786
5683.099
5684.186
5691.955
5699.724
5699.879
5705.55
5711.222
5714.459
5720.241
5726.023
5726.029
5734.422
5742.814
5767.795
5777.164
5786.533
5803.887
5810.076
5816.265
5816.42
5822.763
5829.107
5832.023
5840.458
5848.894
5856.954
5868.25
5879.546
5879.588
5888.744
5897.9
5898.07
5909.769
5921.469
5923.788
5933.502
5943.215
5943.385
5952.758
5962.13
5973.586
5985.249
5996.913
5998.015
6008.576
6019.137
6019.872
6027.31
6034.749
6035.3
6042.831
6050.361
6067.076
6081.127
6095.178
6095.912
6108.218
6120.524
6186.655
6194.454
6202.254
6202.492
6209.862
6217.232
6217.504
6227.514
6237.524
6275.163
6284.15
6293.136
6293.984
6303.479
6312.974
6321.463
6332.667
6343.871
6346.716
6356.381
6366.045
6378.768
6393.095
6407.421
6407.605
6438.187
6468.768
6470.605
6487.319
6504.033
6521.115
6534.982
6548.849
6575.849
6589.257
6602.666
6603.584
6652.9
6702.216
6715.257
6730.594
6745.93
6798.461
6809.114
6819.767
6825.828
6837.675
6849.522
6849.889
6859.44
6868.991
6869.175
6890.297
6911.42
6911.603
6920.971
6930.338
6931.256
6947.144
6963.032
6963.583
6971.113
6978.644
6979.011
6995.266
7011.521
7012.072
7021.072
7030.072
7030.256
7035.123
7039.991
7040.358
7053.491
7066.623
7066.991
7075.623
7084.256
7118.235
7143.949
7169.664
7178.664
7189.317
7199.97
7231.745
7242.949
7254.153
7254.704
7269.031
7283.357
7283.908
7296.949
7309.99
7310.541
7341.306
7372.071
7375.194
7390.071
7404.949
7405.5
7418.632
7431.765
7433.234
7447.101
7460.969
7461.887
7471.622
7481.356
7524.336
7537.193
7550.05
7603.315
7617.366
7631.417
7639.922
7651.028
7662.134
7704.863
7713.35
7721.837
7729.987
7736.204
7742.42
7742.834
7750.915
7758.997
7760.24
7767.769
7775.297
7776.519
7788.917
7801.314
7811.174
7827.282
7843.39
7871.875
7881.201
7890.527
7905.09
7914.09
7923.09
7984.804
7994.906
8005.008
8006.661
8018.691
8030.722
8131.007
8153.048
8175.089
8192.538
8215.68
8238.823
8239.925
8254.895
8269.864
8307.149
8329.925
8352.7
8353.435
8364.455
8375.476
8378.598
8391.272
8403.945
8404.496
8413.955
8423.414
8423.598
8432.965
8442.333
8457.388
8464.68
8471.972
8472.104
8479.131
8486.157
8495.334
8507.712
8520.089
8520.598
8531.958
8543.319
8555.291
8565.118
8574.944
8575.312
8592.026
8608.74
8650.067
8661.913
8673.76
8719.855
8724.498
8729.142
8757.148
8771.291
8785.433
8800.495
8826.76
8853.025
8860.556
8871.76
8882.964
8883.698
8894.811
8905.923
8906.29
8932.096
8957.902
8966.168
8976.729
8987.29
8988.025
8998.678
9009.331
9009.882
9020.259
9030.637
9031.739
9041.657
9051.575
9056.496
9062.396
9068.296
9068.959
9078.57
9088.182
9089.963
9098.136
9106.31
9113.473
9142.493
9171.514
9196.31
9207.881
9219.452
9233.962
9244.34
9254.718
9254.901
9262.891
9270.881
9271.064
9281.258
9291.452
9308.35
9319.83
9331.309
9345.773
9366.207
9386.641
9387.1
9398.694
9410.288
9411.207
9454.025
9496.844
9554.472
9573.413
9592.354
9613.476
9626.563
9639.65
9640.109
9654.688
9669.267
9688.553
9723.565
9758.578
9779.012
9790.95
9802.889
9843.016
9866.062
9889.107
9903.45
9934.33
9965.21
10067.77
10077.87
10087.97
10088.18
10099.92
10111.66
10126.38
10138.78
10151.18
10151.41
10161.74
10172.07
10172.76
10184.81
10196.87
10200.08
10212.14
10224.19
10224.65
10236.01
10247.38
10249.52
10262.23
10274.94
10276.56
10285.67
10294.77
10295.62
10305.69
10315.75
10334.89
10347.33
10359.76
10435.64
10450.45
10465.26
10466.56
10476.95
10487.33
10499.93
10509.8
10519.67
10520.59
10535.4
10550.21
10570.41
10590.04
10609.67
10615.18
10638.37
10661.56
10662.02
10684.4
10706.79
10709.31
10734.45
10759.59
10761.75
10777.84
10793.93
10828.47
10847.99
10867.5
10874.06
10893.68
10913.3
10951.44
10963.37
10975.3
11028.77
11056.4
11084.03
11090.89
11107.43
11123.96
11132.45
11152.43
11172.4
11285.82
11305.1
11324.39
11377.88
11389.94
11401.99
11402.35
11414.43
11426.5
11428.16
11442.74
11457.32
11464.41
11477.66
11490.9
11491.24
11501.47
11511.7
11513.71
11530.99
11548.26
11563.85
11577.63
11591.4
11613
11626.92
11640.84
11643.86
11657.11
11670.36
11670.69
11686.46
11702.22
11719.74
11732.72
11745.69
11746.38
11756.13
11765.89
11769.8
11786.1
11802.4
11822.14
11835.46
11848.77
11867.09
11883.39
11899.68
11900.2
11913.4
11926.61
11927.82
11938.26
11948.69
11949.11
11964.95
11980.79
11980.83
12004.32
12027.8
12064.36
12080.32
12096.27
12266.86
12290.16
12313.47
12436.99
12459.03
12481.07
12546.5
12573.59
12600.69
12601.37
12615.26
12629.15
12661.3
12674.73
12688.16
12723.06
12738.33
12753.59
12769.89
12789.06
12808.24
12830.74
12870.91
12911.09
12937.95
12962.98
12988.01
13049.54
13076.86
13104.18
13119.56
13135.29
13151.02
13259.38
13273.73
13288.08
13304.84
13325.96
13347.09
13349.01
13365.97
13382.93
13510.31
13524.23
13538.16
13598.03
13619.61
13641.19
13700.43
13720.06
13739.69
13739.92
13781.47
13823.03
13826.35
13845.18
13864.02
13864.91
13894.51
13924.11
13925.45
13942.27
13959.08
13959.98
13981.28
14002.58
14008.41
14042.49
14076.57
14077.02
14099.66
14122.31
14124.55
14152.13
14179.7
14180.6
14204.59
14228.58
14229.93
14254.82
14279.7
14280.6
14301.9
14323.2
14412.88
14435.3
14457.73
14464.45
14489.34
14514.23
14516.47
14543.37
14570.28
14571.18
14594.72
14618.26
14707.6
14727.24
14746.88
14764.89
14786.87
14808.84
14859.96
14882.15
14904.35
14951.88
14980.13
15008.38
15519.58
15560.39
15601.2
15717.5
15751.16
15784.83
16261.72
16302.97
16344.23
16447.74
16504.38
16561.02
16607.55
16625.96
16644.36
17771.55
17809.44
17847.33
17971.11
17996.07
18021.03
18021.82
18048.07
18074.32
18248.22
18280.06
18311.89
18594.4
18638.57
18682.74
18811.43
18848.65
18885.87
19822.65
19999.45
20176.24
20808.15
20831.29
20854.43
20873.86
20939.16
21004.45
21006.87
21065.87
21124.88
21125.85
21173.49
21221.13
21221.61
21272.15
21322.7
21323.18
21373.24
21423.3
21636.47
21786.47
21936.48
22991.54
23049.38
23107.22
23107.99
23155.81
23203.63
23205.94
23266.87
23327.8
23404.15
23469.71
23535.26
27895.09
27945.61
27996.12
27999.21
28074.02
28148.83
using the integrated intensity values in a first stage classification algorithm using a training set comprising class-labeled spectra produced from blood-based samples from the same type of cancer patients to identify the patient as being in a class of patients determined to be a poor prognosis subgroup,
(b) identifying the patient as being in the class of patients determined to be a poor prognosis subgroup, using the integrated intensity values as shown in the table in a second stage classification algorithm using a training set comprising class-labeled spectra produced from blood-based samples from the same type of cancer patients treated with an immunotherapy drug to a class label of Late or the equivalent which identifies the patient as likely to have durable benefit from an immunotherapy drug; and
(c) administering to the patient having a class label of Late or the equivalent an immunotherapy drug.
8. The method of claim 7 , wherein the immunotherapy drug comprises an antibody drug blocking ligand activation of the PD-1 checkpoint protein, anti-CTLA4 drugs, high dose interleukin-2, and combination therapies.